TY  - JOUR
AU  - Paskaš, Svetlana
AU  - Stockmann, Philipp
AU  - Mijatović, Sanja
AU  - Kuhnert, Lydia
AU  - Honscha, Walther
AU  - Hey-Hawkins, Evamarie
AU  - Maksimović-Ivanić, Danijela
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6489
AB  - Abstract: The ABCG2 transporter protein, as part of several known mechanisms involved in multidrug
resistance, has the ability to transport a broad spectrum of substrates out of the cell and is,
therefore, considered as a potential target to improve cancer therapies or as an approach to combat
drug resistance in cancer. We have previously reported carborane-functionalized quinazoline derivatives
as potent inhibitors of human ABCG2 which effectively reversed breast cancer resistance protein
(BCRP)-mediated mitoxantrone resistance. In this work, we present the evaluation of our most
promising carboranyl BCRP inhibitors regarding their toxicity towards ABCG2-expressing cancer cell
lines (MCF-7, doxorubicin-resistant MCF-7 or MCF-7 Doxo, HT29, and SW480) and, consequently,
with the co-administration of an inhibitor and therapeutic agent, their ability to increase the efficacy
of therapeutics with the successful inhibition of ABCG2. The results obtained revealed synergistic
effects of several inhibitors in combination with doxorubicin or cisplatin. Compounds DMQCa,
DMQCc, and DMQCd showed a decrease in IC50 value in ABCB1- and ABCG2-expressing SW480
cells, suggesting a possible targeting of both transporters. In an HT29 cell line, with the highest
expression of ABCG2 among the tested cell lines, using co-treatment of doxorubicin and DMQCd, the
effective inhibitory concentration of the antineoplastic agent could be reduced by half. Interestingly,
co-treatment of compound QCe with cisplatin, which is not an ABCG2 substrate, showed synergistic
effects in MCF-7 Doxo and HT29 cells (IC50 values halved or reduced by 20%, respectively). However,
a literature-known upregulation of cisplatin-effluxing ABC transporters and their effective inhibition
by the carborane derivatives emerges as a possible reason.
PB  - Basel: MDPI
T2  - Pharmaceuticals
T1  - Carborane-Based ABCG2-Inhibitors Sensitize ABC-(Over)Expressing Cancer Cell Lines for Doxorubicin and Cisplatin
IS  - 11
VL  - 16
DO  - 10.3390/ph16111582
SP  - 1582
ER  - 

@article{
author = "Paskaš, Svetlana and Stockmann, Philipp and Mijatović, Sanja and Kuhnert, Lydia and Honscha, Walther and Hey-Hawkins, Evamarie and Maksimović-Ivanić, Danijela",
year = "2023",
abstract = "Abstract: The ABCG2 transporter protein, as part of several known mechanisms involved in multidrug
resistance, has the ability to transport a broad spectrum of substrates out of the cell and is,
therefore, considered as a potential target to improve cancer therapies or as an approach to combat
drug resistance in cancer. We have previously reported carborane-functionalized quinazoline derivatives
as potent inhibitors of human ABCG2 which effectively reversed breast cancer resistance protein
(BCRP)-mediated mitoxantrone resistance. In this work, we present the evaluation of our most
promising carboranyl BCRP inhibitors regarding their toxicity towards ABCG2-expressing cancer cell
lines (MCF-7, doxorubicin-resistant MCF-7 or MCF-7 Doxo, HT29, and SW480) and, consequently,
with the co-administration of an inhibitor and therapeutic agent, their ability to increase the efficacy
of therapeutics with the successful inhibition of ABCG2. The results obtained revealed synergistic
effects of several inhibitors in combination with doxorubicin or cisplatin. Compounds DMQCa,
DMQCc, and DMQCd showed a decrease in IC50 value in ABCB1- and ABCG2-expressing SW480
cells, suggesting a possible targeting of both transporters. In an HT29 cell line, with the highest
expression of ABCG2 among the tested cell lines, using co-treatment of doxorubicin and DMQCd, the
effective inhibitory concentration of the antineoplastic agent could be reduced by half. Interestingly,
co-treatment of compound QCe with cisplatin, which is not an ABCG2 substrate, showed synergistic
effects in MCF-7 Doxo and HT29 cells (IC50 values halved or reduced by 20%, respectively). However,
a literature-known upregulation of cisplatin-effluxing ABC transporters and their effective inhibition
by the carborane derivatives emerges as a possible reason.",
publisher = "Basel: MDPI",
journal = "Pharmaceuticals",
title = "Carborane-Based ABCG2-Inhibitors Sensitize ABC-(Over)Expressing Cancer Cell Lines for Doxorubicin and Cisplatin",
number = "11",
volume = "16",
doi = "10.3390/ph16111582",
pages = "1582"
}

Paskaš, S., Stockmann, P., Mijatović, S., Kuhnert, L., Honscha, W., Hey-Hawkins, E.,& Maksimović-Ivanić, D.. (2023). Carborane-Based ABCG2-Inhibitors Sensitize ABC-(Over)Expressing Cancer Cell Lines for Doxorubicin and Cisplatin. in Pharmaceuticals
Basel: MDPI., 16(11), 1582.
https://doi.org/10.3390/ph16111582

Paskaš S, Stockmann P, Mijatović S, Kuhnert L, Honscha W, Hey-Hawkins E, Maksimović-Ivanić D. Carborane-Based ABCG2-Inhibitors Sensitize ABC-(Over)Expressing Cancer Cell Lines for Doxorubicin and Cisplatin. in Pharmaceuticals. 2023;16(11):1582.
doi:10.3390/ph16111582 .

Paskaš, Svetlana, Stockmann, Philipp, Mijatović, Sanja, Kuhnert, Lydia, Honscha, Walther, Hey-Hawkins, Evamarie, Maksimović-Ivanić, Danijela, "Carborane-Based ABCG2-Inhibitors Sensitize ABC-(Over)Expressing Cancer Cell Lines for Doxorubicin and Cisplatin" in Pharmaceuticals, 16, no. 11 (2023):1582,
https://doi.org/10.3390/ph16111582 . .

TY  - JOUR
AU  - Stockmann, Philipp
AU  - Kuhnert, Lydia
AU  - Krajnović, Tamara
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Honscha, Walther
AU  - Hey-Hawkins, Evamarie
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6436
AB  - Multidrug resistance is a major challenge in clinical cancer therapy. In particular, overexpression of certain ATP-binding cassette (ABC) transporter proteins, like the efflux transporter ABCG2, also known as breast cancer resistance protein (BCRP), has been associated with the development of resistance to applied chemotherapeutic agents in cancer therapies, and therefore targeted inhibition of BCRP-mediated transport might lead to reversal of this (multidrug) resistance (MDR). In a previous study, we have described the introduction of a boron-carbon cluster, namely closodicarbadodecaborane or carborane, as an inorganic pharmacophore into a polymethoxylated 2-phenylquinazolin-4-amine backbone. In this work, the scope was extended to the corresponding amide derivatives. As most of the amide derivatives suffered from poor solubility, only the amide derivative QCe and the two amine derivatives DMQCc and DMQCd were further investigated. Carboranes are often considered as sterically demanding phenyl mimetics or isosteres. Therefore, the organic phenyl and sterically demanding adamantyl analogues of the most promising carborane derivatives were also investigated. The studies showed that the previously described DMQCd, a penta-methoxylated N-carboranyl-2phenylquinazolin-4-amine, was by far superior to its organic analogues in terms of cytotoxicity, inhibition of the human ABCG2 transporter, as well as the ability to reverse BCRP-mediated mitoxantrone resistance in MDCKII-hABCG2 and HT29 colon cancer cells. Our results indicate that DMQCd is a promising candidate for further in vitro as well as in vivo studies in combination therapy for ABCG2-overexpressing cancers.
PB  - Wiley-VCH GmbH
T2  - ChemMedChem
T1  - Carboranes as Potent Phenyl Mimetics: A Comparative Study on the Reversal of ABCG2-Mediated Drug Resistance by Carboranylquinazolines and Their Organic Isosteres
DO  - 10.1002/cmdc.202300506
SP  - e202300506
ER  - 

@article{
author = "Stockmann, Philipp and Kuhnert, Lydia and Krajnović, Tamara and Mijatović, Sanja and Maksimović-Ivanić, Danijela and Honscha, Walther and Hey-Hawkins, Evamarie",
year = "2023",
abstract = "Multidrug resistance is a major challenge in clinical cancer therapy. In particular, overexpression of certain ATP-binding cassette (ABC) transporter proteins, like the efflux transporter ABCG2, also known as breast cancer resistance protein (BCRP), has been associated with the development of resistance to applied chemotherapeutic agents in cancer therapies, and therefore targeted inhibition of BCRP-mediated transport might lead to reversal of this (multidrug) resistance (MDR). In a previous study, we have described the introduction of a boron-carbon cluster, namely closodicarbadodecaborane or carborane, as an inorganic pharmacophore into a polymethoxylated 2-phenylquinazolin-4-amine backbone. In this work, the scope was extended to the corresponding amide derivatives. As most of the amide derivatives suffered from poor solubility, only the amide derivative QCe and the two amine derivatives DMQCc and DMQCd were further investigated. Carboranes are often considered as sterically demanding phenyl mimetics or isosteres. Therefore, the organic phenyl and sterically demanding adamantyl analogues of the most promising carborane derivatives were also investigated. The studies showed that the previously described DMQCd, a penta-methoxylated N-carboranyl-2phenylquinazolin-4-amine, was by far superior to its organic analogues in terms of cytotoxicity, inhibition of the human ABCG2 transporter, as well as the ability to reverse BCRP-mediated mitoxantrone resistance in MDCKII-hABCG2 and HT29 colon cancer cells. Our results indicate that DMQCd is a promising candidate for further in vitro as well as in vivo studies in combination therapy for ABCG2-overexpressing cancers.",
publisher = "Wiley-VCH GmbH",
journal = "ChemMedChem",
title = "Carboranes as Potent Phenyl Mimetics: A Comparative Study on the Reversal of ABCG2-Mediated Drug Resistance by Carboranylquinazolines and Their Organic Isosteres",
doi = "10.1002/cmdc.202300506",
pages = "e202300506"
}

Stockmann, P., Kuhnert, L., Krajnović, T., Mijatović, S., Maksimović-Ivanić, D., Honscha, W.,& Hey-Hawkins, E.. (2023). Carboranes as Potent Phenyl Mimetics: A Comparative Study on the Reversal of ABCG2-Mediated Drug Resistance by Carboranylquinazolines and Their Organic Isosteres. in ChemMedChem
Wiley-VCH GmbH., e202300506.
https://doi.org/10.1002/cmdc.202300506

Stockmann P, Kuhnert L, Krajnović T, Mijatović S, Maksimović-Ivanić D, Honscha W, Hey-Hawkins E. Carboranes as Potent Phenyl Mimetics: A Comparative Study on the Reversal of ABCG2-Mediated Drug Resistance by Carboranylquinazolines and Their Organic Isosteres. in ChemMedChem. 2023;:e202300506.
doi:10.1002/cmdc.202300506 .

Stockmann, Philipp, Kuhnert, Lydia, Krajnović, Tamara, Mijatović, Sanja, Maksimović-Ivanić, Danijela, Honscha, Walther, Hey-Hawkins, Evamarie, "Carboranes as Potent Phenyl Mimetics: A Comparative Study on the Reversal of ABCG2-Mediated Drug Resistance by Carboranylquinazolines and Their Organic Isosteres" in ChemMedChem (2023):e202300506,
https://doi.org/10.1002/cmdc.202300506 . .

TY  - JOUR
AU  - Stockmann, Philipp
AU  - Kuhnert, Lydia
AU  - Krajnović, Tamara
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Honscha, Walther
AU  - Hey-Hawkins, Evamarie
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6425
AB  - Multidrug resistance is a major challenge in clinical cancer therapy. In particular, overexpression of certain ATP-binding cassette (ABC) transporter proteins, like the efflux transporter ABCG2, also known as breast cancer resistance protein (BCRP), has been associated with the development of resistance to applied chemotherapeutic agents in cancer therapies, and therefore targeted inhibition of BCRP-mediated transport might lead to reversal of this (multidrug) resistance (MDR). In a previous study, we have described the introduction of a boron-carbon cluster, namely closodicarbadodecaborane or carborane, as an inorganic pharmacophore into a polymethoxylated 2-phenylquinazolin-4-amine backbone. In this work, the scope was extended to the corresponding amide derivatives. As most of the amide derivatives suffered from poor solubility, only the amide derivative QCe and the two amine derivatives DMQCc and DMQCd were further investigated. Carboranes are often considered as sterically demanding phenyl mimetics or isosteres. Therefore, the organic phenyl and sterically demanding adamantyl analogues of the most promising carborane derivatives were also investigated. The studies showed that the previously described DMQCd, a penta-methoxylated N-carboranyl-2phenylquinazolin-4-amine, was by far superior to its organic analogues in terms of cytotoxicity, inhibition of the human ABCG2 transporter, as well as the ability to reverse BCRP-mediated mitoxantrone resistance in MDCKII-hABCG2 and HT29 colon cancer cells. Our results indicate that DMQCd is a promising candidate for further in vitro as well as in vivo studies in combination therapy for ABCG2-overexpressing cancers.
PB  - Wiley-VCH GmbH
T2  - ChemMedChem
T1  - Carboranes as Potent Phenyl Mimetics: A Comparative Study on the Reversal of ABCG2-Mediated Drug Resistance by Carboranylquinazolines and Their Organic Isosteres
DO  - 10.1002/cmdc.202300506
SP  - e202300506
ER  - 

@article{
author = "Stockmann, Philipp and Kuhnert, Lydia and Krajnović, Tamara and Mijatović, Sanja and Maksimović-Ivanić, Danijela and Honscha, Walther and Hey-Hawkins, Evamarie",
year = "2023",
abstract = "Multidrug resistance is a major challenge in clinical cancer therapy. In particular, overexpression of certain ATP-binding cassette (ABC) transporter proteins, like the efflux transporter ABCG2, also known as breast cancer resistance protein (BCRP), has been associated with the development of resistance to applied chemotherapeutic agents in cancer therapies, and therefore targeted inhibition of BCRP-mediated transport might lead to reversal of this (multidrug) resistance (MDR). In a previous study, we have described the introduction of a boron-carbon cluster, namely closodicarbadodecaborane or carborane, as an inorganic pharmacophore into a polymethoxylated 2-phenylquinazolin-4-amine backbone. In this work, the scope was extended to the corresponding amide derivatives. As most of the amide derivatives suffered from poor solubility, only the amide derivative QCe and the two amine derivatives DMQCc and DMQCd were further investigated. Carboranes are often considered as sterically demanding phenyl mimetics or isosteres. Therefore, the organic phenyl and sterically demanding adamantyl analogues of the most promising carborane derivatives were also investigated. The studies showed that the previously described DMQCd, a penta-methoxylated N-carboranyl-2phenylquinazolin-4-amine, was by far superior to its organic analogues in terms of cytotoxicity, inhibition of the human ABCG2 transporter, as well as the ability to reverse BCRP-mediated mitoxantrone resistance in MDCKII-hABCG2 and HT29 colon cancer cells. Our results indicate that DMQCd is a promising candidate for further in vitro as well as in vivo studies in combination therapy for ABCG2-overexpressing cancers.",
publisher = "Wiley-VCH GmbH",
journal = "ChemMedChem",
title = "Carboranes as Potent Phenyl Mimetics: A Comparative Study on the Reversal of ABCG2-Mediated Drug Resistance by Carboranylquinazolines and Their Organic Isosteres",
doi = "10.1002/cmdc.202300506",
pages = "e202300506"
}

Stockmann, P., Kuhnert, L., Krajnović, T., Mijatović, S., Maksimović-Ivanić, D., Honscha, W.,& Hey-Hawkins, E.. (2023). Carboranes as Potent Phenyl Mimetics: A Comparative Study on the Reversal of ABCG2-Mediated Drug Resistance by Carboranylquinazolines and Their Organic Isosteres. in ChemMedChem
Wiley-VCH GmbH., e202300506.
https://doi.org/10.1002/cmdc.202300506

Stockmann P, Kuhnert L, Krajnović T, Mijatović S, Maksimović-Ivanić D, Honscha W, Hey-Hawkins E. Carboranes as Potent Phenyl Mimetics: A Comparative Study on the Reversal of ABCG2-Mediated Drug Resistance by Carboranylquinazolines and Their Organic Isosteres. in ChemMedChem. 2023;:e202300506.
doi:10.1002/cmdc.202300506 .

Stockmann, Philipp, Kuhnert, Lydia, Krajnović, Tamara, Mijatović, Sanja, Maksimović-Ivanić, Danijela, Honscha, Walther, Hey-Hawkins, Evamarie, "Carboranes as Potent Phenyl Mimetics: A Comparative Study on the Reversal of ABCG2-Mediated Drug Resistance by Carboranylquinazolines and Their Organic Isosteres" in ChemMedChem (2023):e202300506,
https://doi.org/10.1002/cmdc.202300506 . .

TY  - JOUR
AU  - Braun, Sebastian
AU  - Paskaš, Svetlana
AU  - Laube, Markus
AU  - George, Sven
AU  - Hofmann, Bettina
AU  - Lönnecke, Peter
AU  - Steinhilber, Dieter
AU  - Pietzsch, Jens
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Hey-Hawkins, Evamarie
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6431
AB  - The presence of inflammatory mediators in the tumor microenvironment,
such as cytokines, growth factors or eicosanoids,
indicate cancer-related inflammatory processes. Targeting these
inflammatory mediators and related signal pathways may offer
a rational strategy for the treatment of cancer. This study
focuses on the incorporation of metabolically stable, sterically
demanding, and hydrophobic dicarba-closo-dodecaboranes
(carboranes) into dual cyclooxygenase-2 (COX-2)/5-lipoxygenase
(5-LO) inhibitors that are key enzymes in the biosynthesis
of eicosanoids. The di-tert-butylphenol derivative tebufelone
represents a selective dual COX-2/5-LO inhibitor. The incorporation
of meta- or para-carborane into the tebufelone scaffold
resulted in eight carborane-based tebufelone analogs that
show no COX inhibition but 5-LO inhibitory activity in vitro. Cell
viability studies on HT29 colon adenocarcinoma cells revealed
that the observed antiproliferative effect of the para-carborane
analogs of tebufelone is enhanced by structural modifications
that include chain elongation in combination with introduction
of a methylene spacer resulting in higher anticancer activity
compared to tebufelone. Hence, this strategy proved to be a
promising approach to design potent 5-LO inhibitors with
potential application as cytostatic agents.
PB  - Wiley-VCH GmbH
T2  - ChemMedChem
T1  - Carborane-Based Tebufelone Analogs and Their Biological Evaluation In Vitro
IS  - 14
VL  - 18
DO  - 10.1002/cmdc.202300206
SP  - e202300206
ER  - 

@article{
author = "Braun, Sebastian and Paskaš, Svetlana and Laube, Markus and George, Sven and Hofmann, Bettina and Lönnecke, Peter and Steinhilber, Dieter and Pietzsch, Jens and Mijatović, Sanja and Maksimović-Ivanić, Danijela and Hey-Hawkins, Evamarie",
year = "2023",
abstract = "The presence of inflammatory mediators in the tumor microenvironment,
such as cytokines, growth factors or eicosanoids,
indicate cancer-related inflammatory processes. Targeting these
inflammatory mediators and related signal pathways may offer
a rational strategy for the treatment of cancer. This study
focuses on the incorporation of metabolically stable, sterically
demanding, and hydrophobic dicarba-closo-dodecaboranes
(carboranes) into dual cyclooxygenase-2 (COX-2)/5-lipoxygenase
(5-LO) inhibitors that are key enzymes in the biosynthesis
of eicosanoids. The di-tert-butylphenol derivative tebufelone
represents a selective dual COX-2/5-LO inhibitor. The incorporation
of meta- or para-carborane into the tebufelone scaffold
resulted in eight carborane-based tebufelone analogs that
show no COX inhibition but 5-LO inhibitory activity in vitro. Cell
viability studies on HT29 colon adenocarcinoma cells revealed
that the observed antiproliferative effect of the para-carborane
analogs of tebufelone is enhanced by structural modifications
that include chain elongation in combination with introduction
of a methylene spacer resulting in higher anticancer activity
compared to tebufelone. Hence, this strategy proved to be a
promising approach to design potent 5-LO inhibitors with
potential application as cytostatic agents.",
publisher = "Wiley-VCH GmbH",
journal = "ChemMedChem",
title = "Carborane-Based Tebufelone Analogs and Their Biological Evaluation In Vitro",
number = "14",
volume = "18",
doi = "10.1002/cmdc.202300206",
pages = "e202300206"
}

Braun, S., Paskaš, S., Laube, M., George, S., Hofmann, B., Lönnecke, P., Steinhilber, D., Pietzsch, J., Mijatović, S., Maksimović-Ivanić, D.,& Hey-Hawkins, E.. (2023). Carborane-Based Tebufelone Analogs and Their Biological Evaluation In Vitro. in ChemMedChem
Wiley-VCH GmbH., 18(14), e202300206.
https://doi.org/10.1002/cmdc.202300206

Braun S, Paskaš S, Laube M, George S, Hofmann B, Lönnecke P, Steinhilber D, Pietzsch J, Mijatović S, Maksimović-Ivanić D, Hey-Hawkins E. Carborane-Based Tebufelone Analogs and Their Biological Evaluation In Vitro. in ChemMedChem. 2023;18(14):e202300206.
doi:10.1002/cmdc.202300206 .

Braun, Sebastian, Paskaš, Svetlana, Laube, Markus, George, Sven, Hofmann, Bettina, Lönnecke, Peter, Steinhilber, Dieter, Pietzsch, Jens, Mijatović, Sanja, Maksimović-Ivanić, Danijela, Hey-Hawkins, Evamarie, "Carborane-Based Tebufelone Analogs and Their Biological Evaluation In Vitro" in ChemMedChem, 18, no. 14 (2023):e202300206,
https://doi.org/10.1002/cmdc.202300206 . .

TY  - JOUR
AU  - Kazimir, Aleksandr
AU  - Schwarze, Benedikt
AU  - Lönnecke, Peter
AU  - Jelača, Sanja
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Hey-Hawkins, Evamarie
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6266
AB  - For decades, tamoxifen-based hormone therapy has effectively addressed oestrogen receptor positive (ER+) luminal A breast cancer. Nonetheless, the emergence of tamoxifen resistance required innovative
approaches, leading to hybrid metallodrugs with several therapeutic effects besides the inhibition of oestrogen receptor α (ERα). Drawing inspiration from tamoxifen metabolite structures (4-hydroxytamoxifen
and 4,4′-dihyroxytamoxifen), a phenyl ring was replaced by a bidentate 2,2′-bipyridine donor moiety to give
4-[1,1-bis(4-methoxyphenyl)but-1-en-2-yl]-2,2′-bipyridine (L), enabling coordination of bioactive transition
metal compounds such as copper(II) dichloride, yielding [CuCl(μ-Cl)(L-κ2N,N′)]2 (1). Notably, copper(II)
complex 1 exhibited remarkable activity within the low micromolar concentration range against ER+ human glioblastoma U251, as well as breast carcinomas MDA-MB-361 and MCF-7, surpassing the efficacy of previously reported palladium(II) and platinum(II) dichloride analogs against these cell lines. The pronounced efficacy of complex 1 against triple-negative MDA-MB-231 cells highlights its potential multitherapeutic approach, evident through induction of apoptosis and antioxidant activity. This study evaluates the potential of copper–tamoxifen hybrid complex 1 as a potent therapeutic candidate, highlighting its diverse mechanism of action against challenging breast cancer subtypes.
PB  - Royal Society of Chemistry
T2  - RSC Medicinal Chemistry
T1  - Exploring the potential of tamoxifen-based copper(II) dichloride in breast cancer therapy
DO  - 10.1039/d3md00344b
ER  - 

@article{
author = "Kazimir, Aleksandr and Schwarze, Benedikt and Lönnecke, Peter and Jelača, Sanja and Mijatović, Sanja and Maksimović-Ivanić, Danijela and Hey-Hawkins, Evamarie",
year = "2023",
abstract = "For decades, tamoxifen-based hormone therapy has effectively addressed oestrogen receptor positive (ER+) luminal A breast cancer. Nonetheless, the emergence of tamoxifen resistance required innovative
approaches, leading to hybrid metallodrugs with several therapeutic effects besides the inhibition of oestrogen receptor α (ERα). Drawing inspiration from tamoxifen metabolite structures (4-hydroxytamoxifen
and 4,4′-dihyroxytamoxifen), a phenyl ring was replaced by a bidentate 2,2′-bipyridine donor moiety to give
4-[1,1-bis(4-methoxyphenyl)but-1-en-2-yl]-2,2′-bipyridine (L), enabling coordination of bioactive transition
metal compounds such as copper(II) dichloride, yielding [CuCl(μ-Cl)(L-κ2N,N′)]2 (1). Notably, copper(II)
complex 1 exhibited remarkable activity within the low micromolar concentration range against ER+ human glioblastoma U251, as well as breast carcinomas MDA-MB-361 and MCF-7, surpassing the efficacy of previously reported palladium(II) and platinum(II) dichloride analogs against these cell lines. The pronounced efficacy of complex 1 against triple-negative MDA-MB-231 cells highlights its potential multitherapeutic approach, evident through induction of apoptosis and antioxidant activity. This study evaluates the potential of copper–tamoxifen hybrid complex 1 as a potent therapeutic candidate, highlighting its diverse mechanism of action against challenging breast cancer subtypes.",
publisher = "Royal Society of Chemistry",
journal = "RSC Medicinal Chemistry",
title = "Exploring the potential of tamoxifen-based copper(II) dichloride in breast cancer therapy",
doi = "10.1039/d3md00344b"
}

Kazimir, A., Schwarze, B., Lönnecke, P., Jelača, S., Mijatović, S., Maksimović-Ivanić, D.,& Hey-Hawkins, E.. (2023). Exploring the potential of tamoxifen-based copper(II) dichloride in breast cancer therapy. in RSC Medicinal Chemistry
Royal Society of Chemistry..
https://doi.org/10.1039/d3md00344b

Kazimir A, Schwarze B, Lönnecke P, Jelača S, Mijatović S, Maksimović-Ivanić D, Hey-Hawkins E. Exploring the potential of tamoxifen-based copper(II) dichloride in breast cancer therapy. in RSC Medicinal Chemistry. 2023;.
doi:10.1039/d3md00344b .

Kazimir, Aleksandr, Schwarze, Benedikt, Lönnecke, Peter, Jelača, Sanja, Mijatović, Sanja, Maksimović-Ivanić, Danijela, Hey-Hawkins, Evamarie, "Exploring the potential of tamoxifen-based copper(II) dichloride in breast cancer therapy" in RSC Medicinal Chemistry (2023),
https://doi.org/10.1039/d3md00344b . .

TY  - JOUR
AU  - Richter, Stefan
AU  - Lönnecke, Peter
AU  - Bovan, Dijana
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Kaluđerović, Goran N.
AU  - Hey-Hawkins, Evamarie
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6265
AB  - The coordination behavior of three ligand precursors 2-[(2-pyridinylmethyl)amino]acetic acid hydrochloride, 4-[(2-pyridinylmethyl)amino]benzoic acid hydrochloride and 4-{[2-(pyridin-2-ylmethylamino)ethylamino]methyl}benzoic acid hydrochloride, HL1∙HCl–HL3∙HCl, respectively, in copper(II) complexes is described. The complexes were characterized by elemental analysis, ESI mass spectrometry and IR spectroscopy, as well as X-ray structural analysis. The reaction of copper(II) with HL1∙HCl in methanol afforded the polymeric complex [{Cu(µ-Cl)2(MeL1-κ2N,N’)}n] (1) featuring the methyl ester of L1 (MeL1). With HL2∙HCl or HL3∙HCl, the dimeric complex [{CuCl(µ-Cl)(HL2-κ2N,N’)}2] (2) or the mononuclear complex [CuCl2(HL3-κ3N,N’,N’’)] (3) were obtained. All complexes exhibited square-pyramidal geometries. In 1, polymeric chains are formed through bridging chlorido ligands without typical hydrogen bonding interaction. Contrarily, the COOH group in 2 is participating in the formation of intermolecular hydrogen bonding forming a supramolecular structure. In 3, intermolecular hydrogen bonding (Cl…O) leads to a 1-D polymeric structure. The copper(II) complex 2 diminished viability of human 8505C, MCF-7, 518A2 and SW480 cell lines. The tumoricidal effect of 2 was realized mainly through caspase-mediated apoptosis.
PB  - Belgrade: Serbian Chemical Society
T2  - Journal of the Serbian Chemical Society
T1  - Square-pyramidal mononuclear, dinuclear and polymeric copper(II) complexes with (2-pyridinylmethyl)amino derivatives
DO  - 10.2298/JSC230818072R
ER  - 

@article{
author = "Richter, Stefan and Lönnecke, Peter and Bovan, Dijana and Mijatović, Sanja and Maksimović-Ivanić, Danijela and Kaluđerović, Goran N. and Hey-Hawkins, Evamarie",
year = "2023",
abstract = "The coordination behavior of three ligand precursors 2-[(2-pyridinylmethyl)amino]acetic acid hydrochloride, 4-[(2-pyridinylmethyl)amino]benzoic acid hydrochloride and 4-{[2-(pyridin-2-ylmethylamino)ethylamino]methyl}benzoic acid hydrochloride, HL1∙HCl–HL3∙HCl, respectively, in copper(II) complexes is described. The complexes were characterized by elemental analysis, ESI mass spectrometry and IR spectroscopy, as well as X-ray structural analysis. The reaction of copper(II) with HL1∙HCl in methanol afforded the polymeric complex [{Cu(µ-Cl)2(MeL1-κ2N,N’)}n] (1) featuring the methyl ester of L1 (MeL1). With HL2∙HCl or HL3∙HCl, the dimeric complex [{CuCl(µ-Cl)(HL2-κ2N,N’)}2] (2) or the mononuclear complex [CuCl2(HL3-κ3N,N’,N’’)] (3) were obtained. All complexes exhibited square-pyramidal geometries. In 1, polymeric chains are formed through bridging chlorido ligands without typical hydrogen bonding interaction. Contrarily, the COOH group in 2 is participating in the formation of intermolecular hydrogen bonding forming a supramolecular structure. In 3, intermolecular hydrogen bonding (Cl…O) leads to a 1-D polymeric structure. The copper(II) complex 2 diminished viability of human 8505C, MCF-7, 518A2 and SW480 cell lines. The tumoricidal effect of 2 was realized mainly through caspase-mediated apoptosis.",
publisher = "Belgrade: Serbian Chemical Society",
journal = "Journal of the Serbian Chemical Society",
title = "Square-pyramidal mononuclear, dinuclear and polymeric copper(II) complexes with (2-pyridinylmethyl)amino derivatives",
doi = "10.2298/JSC230818072R"
}

Richter, S., Lönnecke, P., Bovan, D., Mijatović, S., Maksimović-Ivanić, D., Kaluđerović, G. N.,& Hey-Hawkins, E.. (2023). Square-pyramidal mononuclear, dinuclear and polymeric copper(II) complexes with (2-pyridinylmethyl)amino derivatives. in Journal of the Serbian Chemical Society
Belgrade: Serbian Chemical Society..
https://doi.org/10.2298/JSC230818072R

Richter S, Lönnecke P, Bovan D, Mijatović S, Maksimović-Ivanić D, Kaluđerović GN, Hey-Hawkins E. Square-pyramidal mononuclear, dinuclear and polymeric copper(II) complexes with (2-pyridinylmethyl)amino derivatives. in Journal of the Serbian Chemical Society. 2023;.
doi:10.2298/JSC230818072R .

Richter, Stefan, Lönnecke, Peter, Bovan, Dijana, Mijatović, Sanja, Maksimović-Ivanić, Danijela, Kaluđerović, Goran N., Hey-Hawkins, Evamarie, "Square-pyramidal mononuclear, dinuclear and polymeric copper(II) complexes with (2-pyridinylmethyl)amino derivatives" in Journal of the Serbian Chemical Society (2023),
https://doi.org/10.2298/JSC230818072R . .

TY  - CONF
AU  - Murganić, Blagoje
AU  - Kazimir, Aleksandr
AU  - Jelača, Sanja
AU  - Tanić, Nikola
AU  - Tanić, Nasta
AU  - Hey-Hawkins, Evamarie
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6261
AB  - Рак дојке је најчешћи облик рака код жена са приближно 70% случајева који су
позитивни на хормонске рецепторе (HR+). Прекомерна експресија естрогенског
рецептора (ER) је уско повезана са пролиферацијом тумора. Антиестрогенске те-
рапије, нпр. са тамоксифеном, су уобичајени и ефикасни приступи у лечењу ЕR+
рака дојке. Иако терапија тамоксифеном спада у групу циљаних терапија, његова
ефикасност је доказана и код хормон-независних типова карцинома дојке, што
указује на присуство других интрацелуларних циљних молекула. Иако је тамок-
сифен показао значајну ефикасност у лечењу ER-позитивних карцинома дојке,
бројни пацијенти су развили резистенцију. У циљу повећања његовог потенци-
јала и превазилажења резистенције, тамоксифен је модификован металима као
што су платина (Pt) и паладијум (Pd). Једињења заснована на Pt традиционално
се користе у хемиотерапији, док комплекси Pd могу смањити токсичност и бити
ефикаснији против одређених врста рака. Циљ ове студије био је да се процени
ефикасност тамоксифена модификованог са Pt и Pd на панелу ћелијских линија
рака дојке са различитим статусом експресије рецептора. Дериват тамоксифена
који се користи као лиганд, смањио је вијабилност туморских ћелија независно
од експресије ER, што указује да се његово антитуморско дејство може превас-
ходно приписати ER-независном деловању. Експериментални лекови су изазвали
апоптозу независну од каспаза, са израженијим ефектом у случају деривата на
бази Pd. Ефикасност деривата Pd може се додатно повећати укидањем процеса
аутофагије. Узето заједно, дериватизација тамоксифена је обећавајућа стратегија
у дизајну хибридних молекула.
AB  - Breast cancer is the most prevalent form of cancer in women, with approximately
70% of cases being hormone receptor positive (HR+). While overexpression of estrogen
receptor (ER) is closely related with tumor proliferation, anti-estrogen therapies,
e.g., with tamoxifen, are common and effective approaches. Although treatment with
tamoxifen belongs to the group of targeted therapies, its effectiveness has also been
proven in hormone-independent types of breast cancer, which indicates the presence
of intracellular off-targets. Apart of the fact that tamoxifen showed significant
efficiency in the treatment of ER+ breast cancers, numerous patients developed resistance
towards it. With an aim to amplify its potential and overcome resistance, tamoxifen
has been modified with transition metals such as platinum (Pt) and palladium
(Pd). Pt-based compounds have traditionally been used in cancer chemotherapy,
while Pd complexes may lower the toxicity and be more effective against certain types
of cancer. The aim of this study was to evaluate the efficacy of tamoxifen modified
with Pt and Pd on a panel of breast cancer cell lines with different receptor expression
status. The tamoxifen derivative used as ligand diminished the viability of tumor cells
independently of ER expression, indicating that its antitumor action can be dominantly
ascribed to a ER-independent action. The experimental drugs induced caspase
independent apoptosis, with a more pronounced effect in the case of the Pd-based
derivatives. The efficacy of the Pd derivate can be further increased by abolishment
of the autophagic process. Taken together, derivatization of tamoxifen is a promising
strategy for hybrid molecule design.
PB  - Kragujevac: Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine
C3  - Abstract Book: The second Serbian Molecular Medicine Congress; 2023 Oct 6-8; Foča, Bosnia and Herzegovina
T1  - Tамоксифен као вектор за платинске(II) и паладијумске(II) комплексе у третману рака дојке
T1  - Tamoxifen as a vector for platinum(II) and palladium(II) complexes in breast cancer treatment
SP  - 18
EP  - 19
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6261
ER  - 

@conference{
author = "Murganić, Blagoje and Kazimir, Aleksandr and Jelača, Sanja and Tanić, Nikola and Tanić, Nasta and Hey-Hawkins, Evamarie and Mijatović, Sanja and Maksimović-Ivanić, Danijela",
year = "2023",
abstract = "Рак дојке је најчешћи облик рака код жена са приближно 70% случајева који су
позитивни на хормонске рецепторе (HR+). Прекомерна експресија естрогенског
рецептора (ER) је уско повезана са пролиферацијом тумора. Антиестрогенске те-
рапије, нпр. са тамоксифеном, су уобичајени и ефикасни приступи у лечењу ЕR+
рака дојке. Иако терапија тамоксифеном спада у групу циљаних терапија, његова
ефикасност је доказана и код хормон-независних типова карцинома дојке, што
указује на присуство других интрацелуларних циљних молекула. Иако је тамок-
сифен показао значајну ефикасност у лечењу ER-позитивних карцинома дојке,
бројни пацијенти су развили резистенцију. У циљу повећања његовог потенци-
јала и превазилажења резистенције, тамоксифен је модификован металима као
што су платина (Pt) и паладијум (Pd). Једињења заснована на Pt традиционално
се користе у хемиотерапији, док комплекси Pd могу смањити токсичност и бити
ефикаснији против одређених врста рака. Циљ ове студије био је да се процени
ефикасност тамоксифена модификованог са Pt и Pd на панелу ћелијских линија
рака дојке са различитим статусом експресије рецептора. Дериват тамоксифена
који се користи као лиганд, смањио је вијабилност туморских ћелија независно
од експресије ER, што указује да се његово антитуморско дејство може превас-
ходно приписати ER-независном деловању. Експериментални лекови су изазвали
апоптозу независну од каспаза, са израженијим ефектом у случају деривата на
бази Pd. Ефикасност деривата Pd може се додатно повећати укидањем процеса
аутофагије. Узето заједно, дериватизација тамоксифена је обећавајућа стратегија
у дизајну хибридних молекула., Breast cancer is the most prevalent form of cancer in women, with approximately
70% of cases being hormone receptor positive (HR+). While overexpression of estrogen
receptor (ER) is closely related with tumor proliferation, anti-estrogen therapies,
e.g., with tamoxifen, are common and effective approaches. Although treatment with
tamoxifen belongs to the group of targeted therapies, its effectiveness has also been
proven in hormone-independent types of breast cancer, which indicates the presence
of intracellular off-targets. Apart of the fact that tamoxifen showed significant
efficiency in the treatment of ER+ breast cancers, numerous patients developed resistance
towards it. With an aim to amplify its potential and overcome resistance, tamoxifen
has been modified with transition metals such as platinum (Pt) and palladium
(Pd). Pt-based compounds have traditionally been used in cancer chemotherapy,
while Pd complexes may lower the toxicity and be more effective against certain types
of cancer. The aim of this study was to evaluate the efficacy of tamoxifen modified
with Pt and Pd on a panel of breast cancer cell lines with different receptor expression
status. The tamoxifen derivative used as ligand diminished the viability of tumor cells
independently of ER expression, indicating that its antitumor action can be dominantly
ascribed to a ER-independent action. The experimental drugs induced caspase
independent apoptosis, with a more pronounced effect in the case of the Pd-based
derivatives. The efficacy of the Pd derivate can be further increased by abolishment
of the autophagic process. Taken together, derivatization of tamoxifen is a promising
strategy for hybrid molecule design.",
publisher = "Kragujevac: Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine",
journal = "Abstract Book: The second Serbian Molecular Medicine Congress; 2023 Oct 6-8; Foča, Bosnia and Herzegovina",
title = "Tамоксифен као вектор за платинске(II) и паладијумске(II) комплексе у третману рака дојке, Tamoxifen as a vector for platinum(II) and palladium(II) complexes in breast cancer treatment",
pages = "18-19",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6261"
}

Murganić, B., Kazimir, A., Jelača, S., Tanić, N., Tanić, N., Hey-Hawkins, E., Mijatović, S.,& Maksimović-Ivanić, D.. (2023). Tамоксифен као вектор за платинске(II) и паладијумске(II) комплексе у третману рака дојке. in Abstract Book: The second Serbian Molecular Medicine Congress; 2023 Oct 6-8; Foča, Bosnia and Herzegovina
Kragujevac: Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine., 18-19.
https://hdl.handle.net/21.15107/rcub_ibiss_6261

Murganić B, Kazimir A, Jelača S, Tanić N, Tanić N, Hey-Hawkins E, Mijatović S, Maksimović-Ivanić D. Tамоксифен као вектор за платинске(II) и паладијумске(II) комплексе у третману рака дојке. in Abstract Book: The second Serbian Molecular Medicine Congress; 2023 Oct 6-8; Foča, Bosnia and Herzegovina. 2023;:18-19.
https://hdl.handle.net/21.15107/rcub_ibiss_6261 .

Murganić, Blagoje, Kazimir, Aleksandr, Jelača, Sanja, Tanić, Nikola, Tanić, Nasta, Hey-Hawkins, Evamarie, Mijatović, Sanja, Maksimović-Ivanić, Danijela, "Tамоксифен као вектор за платинске(II) и паладијумске(II) комплексе у третману рака дојке" in Abstract Book: The second Serbian Molecular Medicine Congress; 2023 Oct 6-8; Foča, Bosnia and Herzegovina (2023):18-19,
https://hdl.handle.net/21.15107/rcub_ibiss_6261 .

TY  - CONF
AU  - Jelača, Sanja
AU  - Braun, Sebastian
AU  - Mijatović, Sanja
AU  - Hey-Hawkins, Evamarie
AU  - Maksimović-Ivanić, Danijela
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6260
AB  - Tаргетовање медијатора инфламације као што су циклооксигеназа-2 (COX) и 5-липоксигеназа (5-LO) може бити обећавајућа стратегија у лечењу канцера. У циљу побољшања селективности, карборан је уграђен у комерцијалне двоструке инхибиторе COX-2/5-LО. У овој студији, процењена је антитуморска активност деривата di-tert-бутилфенола (R-830, KME-4, E-5110, and S-2474) и њихових одговарајућих аналога карборана (R-830-Cb, KME-4-Cb, E-5110-Cb, S-2474-Cb) на панелу хуманих ћелијских линија рака (A375, A549, HCT116, HT-29, and MDA-MB-231). Третман дериватима
di-tert-бутилфенола смањио је вијабилност свих ћелија рака на дозно зависан начин након 72 h. Истовремено, уградња p-карборан групе је резултирала смањењем цитотоксичног потенцијала за све тестиране аналоге карборана, осим R-830-Cb. Стога су за даље испитивање потенцијалног механизма деловања одабрани R-830 и његов карборан аналог R-830-Cb. За разлику од R-830, његов карборански пандан није утицао на вијабилитет ћелија примарног перитонеалног ексудата, што указује да је уградња карборана побољшала селективност према малигном фенотипу. Смањење вијабилности туморских ћелија изазвано R-830-Cb је праћено губитком дeoбног потенцијала, док је одређени проценат HCT116 ћелија био подвргнут програмираној ћелијској
смрти зависном од каспаза. Паралелно, флуоресцентна микроскопија је открила присуство бројних ћелија са абнормалним нуклеусима и кондензованим хроматином. Даље, обустављање аутофагије употребом инхибитора аутофагије 3-метил аденина (3-МА) и хлорокина, открило је цитопротективну улогу овог процеса, компромитујући активност лека. Сви уочени ефекти били су праћени смањеном производњом реактивних врста кисеоника и азота (ROS/RNS) што указује на поремећен редокс
статус ћелија као одговор на третман. Узевши заједно, аналог R-830-Cb на бази карборана је обећавајући кандидат за даљу процену антитуморског ефекта in vivo.
AB  - Targeting inflammatory mediators, such as cyclooxygenase-2 (COX) and 5-lipoxygenase
(5-LO), may be a promising strategy for the treatment of cancer. To improve the selectivity,
a carborane moiety was incorporated into known dual COX-2/5-LO inhibitors. In the
present study, we have evaluated the antitumor activity of di-tert-butylphenol derivatives
(R-830, KME-4, E-5110, and S-2474) and their respective p-carborane analogs (R-830-Cb,
KME-4-Cb, E-5110-Cb, and S-2474-Cb) on a panel of human cancer cell lines (A375, A549,
HCT116, HT-29, and MDA-MB-231). Treatment with di-tert-butylphenol derivatives decreased
the viability of all cancer cells in a dose-dependent manner after 72 h. At the same
time, incorporation of a p-carborane moiety resulted in diminished cytotoxic potential for
all tested carborane analogs, except R-830-Cb. Thus, for further investigation of the potential
mechanism of action, R-830 and its p-carborane analog R-830-Cb were selected. Differently
to R-830, its carborane counterpart did not affect the viability of primary peritoneal exudate
cells, indicating that incorporation of the carborane cage improved selectivity toward
the malignant phenotype. Tumor cell viability decrease triggered by R-830-Cb was followed
by a loss of dividing potential, while a certain percentage of HCT116 cells was subjected
to caspase-dependent programmed cell death. In parallel, fluorescent microscopy revealed
the presence of numerous cells with abnormally shaped nuclei and condensed chromatin.
Furthermore, abolishment of the autophagy using autophagy inhibitors 3-methyladenine
(3-MA) and chloroquine, revealed a cytoprotective role of this process, compromising the
activity of the drug. All observed effects were accompanied by reduced production of reactive
oxygen and nitrogen species (ROS/RNS) indicating a disturbed redox status of the cells
in response to the treatment. Taken together, carborane-based analog R-830-Cb is a promising
candidate for further assessment of the antitumor effect in vivo.
PB  - Kragujevac: Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine
C3  - Abstract Book: The second Serbian Molecular Medicine Congress; 2023 Oct 6-8; Foča, Bosnia and Herzegovina
T1  - In vitro биолошка евалуација аналога di-tert-бутилфенола на бази p-карборана
T1  - In vitro biological evaluation of p-carborane-based di-tert-butylphenol analogs
SP  - 79
EP  - 80
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6260
ER  - 

@conference{
author = "Jelača, Sanja and Braun, Sebastian and Mijatović, Sanja and Hey-Hawkins, Evamarie and Maksimović-Ivanić, Danijela",
year = "2023",
abstract = "Tаргетовање медијатора инфламације као што су циклооксигеназа-2 (COX) и 5-липоксигеназа (5-LO) може бити обећавајућа стратегија у лечењу канцера. У циљу побољшања селективности, карборан је уграђен у комерцијалне двоструке инхибиторе COX-2/5-LО. У овој студији, процењена је антитуморска активност деривата di-tert-бутилфенола (R-830, KME-4, E-5110, and S-2474) и њихових одговарајућих аналога карборана (R-830-Cb, KME-4-Cb, E-5110-Cb, S-2474-Cb) на панелу хуманих ћелијских линија рака (A375, A549, HCT116, HT-29, and MDA-MB-231). Третман дериватима
di-tert-бутилфенола смањио је вијабилност свих ћелија рака на дозно зависан начин након 72 h. Истовремено, уградња p-карборан групе је резултирала смањењем цитотоксичног потенцијала за све тестиране аналоге карборана, осим R-830-Cb. Стога су за даље испитивање потенцијалног механизма деловања одабрани R-830 и његов карборан аналог R-830-Cb. За разлику од R-830, његов карборански пандан није утицао на вијабилитет ћелија примарног перитонеалног ексудата, што указује да је уградња карборана побољшала селективност према малигном фенотипу. Смањење вијабилности туморских ћелија изазвано R-830-Cb је праћено губитком дeoбног потенцијала, док је одређени проценат HCT116 ћелија био подвргнут програмираној ћелијској
смрти зависном од каспаза. Паралелно, флуоресцентна микроскопија је открила присуство бројних ћелија са абнормалним нуклеусима и кондензованим хроматином. Даље, обустављање аутофагије употребом инхибитора аутофагије 3-метил аденина (3-МА) и хлорокина, открило је цитопротективну улогу овог процеса, компромитујући активност лека. Сви уочени ефекти били су праћени смањеном производњом реактивних врста кисеоника и азота (ROS/RNS) што указује на поремећен редокс
статус ћелија као одговор на третман. Узевши заједно, аналог R-830-Cb на бази карборана је обећавајући кандидат за даљу процену антитуморског ефекта in vivo., Targeting inflammatory mediators, such as cyclooxygenase-2 (COX) and 5-lipoxygenase
(5-LO), may be a promising strategy for the treatment of cancer. To improve the selectivity,
a carborane moiety was incorporated into known dual COX-2/5-LO inhibitors. In the
present study, we have evaluated the antitumor activity of di-tert-butylphenol derivatives
(R-830, KME-4, E-5110, and S-2474) and their respective p-carborane analogs (R-830-Cb,
KME-4-Cb, E-5110-Cb, and S-2474-Cb) on a panel of human cancer cell lines (A375, A549,
HCT116, HT-29, and MDA-MB-231). Treatment with di-tert-butylphenol derivatives decreased
the viability of all cancer cells in a dose-dependent manner after 72 h. At the same
time, incorporation of a p-carborane moiety resulted in diminished cytotoxic potential for
all tested carborane analogs, except R-830-Cb. Thus, for further investigation of the potential
mechanism of action, R-830 and its p-carborane analog R-830-Cb were selected. Differently
to R-830, its carborane counterpart did not affect the viability of primary peritoneal exudate
cells, indicating that incorporation of the carborane cage improved selectivity toward
the malignant phenotype. Tumor cell viability decrease triggered by R-830-Cb was followed
by a loss of dividing potential, while a certain percentage of HCT116 cells was subjected
to caspase-dependent programmed cell death. In parallel, fluorescent microscopy revealed
the presence of numerous cells with abnormally shaped nuclei and condensed chromatin.
Furthermore, abolishment of the autophagy using autophagy inhibitors 3-methyladenine
(3-MA) and chloroquine, revealed a cytoprotective role of this process, compromising the
activity of the drug. All observed effects were accompanied by reduced production of reactive
oxygen and nitrogen species (ROS/RNS) indicating a disturbed redox status of the cells
in response to the treatment. Taken together, carborane-based analog R-830-Cb is a promising
candidate for further assessment of the antitumor effect in vivo.",
publisher = "Kragujevac: Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine",
journal = "Abstract Book: The second Serbian Molecular Medicine Congress; 2023 Oct 6-8; Foča, Bosnia and Herzegovina",
title = "In vitro биолошка евалуација аналога di-tert-бутилфенола на бази p-карборана, In vitro biological evaluation of p-carborane-based di-tert-butylphenol analogs",
pages = "79-80",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6260"
}

Jelača, S., Braun, S., Mijatović, S., Hey-Hawkins, E.,& Maksimović-Ivanić, D.. (2023). In vitro биолошка евалуација аналога di-tert-бутилфенола на бази p-карборана. in Abstract Book: The second Serbian Molecular Medicine Congress; 2023 Oct 6-8; Foča, Bosnia and Herzegovina
Kragujevac: Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine., 79-80.
https://hdl.handle.net/21.15107/rcub_ibiss_6260

Jelača S, Braun S, Mijatović S, Hey-Hawkins E, Maksimović-Ivanić D. In vitro биолошка евалуација аналога di-tert-бутилфенола на бази p-карборана. in Abstract Book: The second Serbian Molecular Medicine Congress; 2023 Oct 6-8; Foča, Bosnia and Herzegovina. 2023;:79-80.
https://hdl.handle.net/21.15107/rcub_ibiss_6260 .

Jelača, Sanja, Braun, Sebastian, Mijatović, Sanja, Hey-Hawkins, Evamarie, Maksimović-Ivanić, Danijela, "In vitro биолошка евалуација аналога di-tert-бутилфенола на бази p-карборана" in Abstract Book: The second Serbian Molecular Medicine Congress; 2023 Oct 6-8; Foča, Bosnia and Herzegovina (2023):79-80,
https://hdl.handle.net/21.15107/rcub_ibiss_6260 .

TY  - CONF
AU  - Komazec, Teodora
AU  - Useini, Liridona
AU  - Mijatović, Sanja
AU  - Hey-Hawkins, Evamarie
AU  - Maksimović-Ivanić, Danijela
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6259
AB  - Нестероидни антиинфламаторни лекови (НСАИЛ) у које између осталог
спада нимесулид показали су антитуморски ефекат против различитих типо-
ва туморских ћелијских линија. Потенцијални цитотоксични ефекат изониме-
сулида, члана породице нимесулида, и његових деривата карборана одређен је
на HT29, HCT116, MCF-7, А375 и А549 хуманим ћелијским линијама. Вијабил-
ност свих тестираних ћелијских линија је дозно-зависно смањена, што је по-
казано МТТ и CV тестовима. Селективност ових једињења према туморском
фенотипу је показана на МRC-5 ћелијама и ћелијама перитонеалног ексудата
мишa, под идентичним експерименталним условима. Проточна цитофлуото-
метријска анализа је открила значајно смањење деобног потенцијала МCF-7
ћелија, након третмана изонимесулидом и његовим одабраним дериватима
карборана (4а и 4б). Показано је да су карборански деривати изонимесулида
изазвали снажну апоптозу која није била посредована активацијом каспазе.
Са друге стране, изонимесулид је покренуо апоптозу посредовану активаци-
јом каспаза и смањио пролиферацију знатно нижом стопом од његових кар-
боранскх деривата. У даљем истраживању апоптозу потврђујемо пропидијум
јодид бојењем МCF-7 ћелија применом флуоресцентне микроскопије. Код
третираних ћелија уочавамо интензивну апоптозу која се манифестује непра-
вилним обликом једара и кондензацијом хроматина. Коначно, инхибирана
производња реактивних врста кисеоника и азота примећена је само у случају
деривата 4б. Нове карактеристике изонимесулида и његових деривата карбо-
рана огледају се у њиховом снажном антитуморном потенцијалу, што отвара
бројне могућности за даља истраживања.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) such as nimesulide have shown
antitumor effects against different types of tumor cell lines. The potential cytotoxic effect
of isonimesulide, a member of the nimesulide family, and its carborane derivatives
was determined against HT29, HCT116, MCF-7, A375, and A549 human cell lines. The
viability of all tested cell lines was dose-dependently decreased as shown by 3-(4,5-dimethythiazol-
2-yl)-2,5-diphenyltetrazolium bromide and crystal violet assays. The selectivity
of these compounds toward a tumor phenotype was demonstrated on MRC-5
and peritoneal exudate cells under identical experimental conditions. Flow cytometric
analysis revealed a significant reduction in the division potential of MCF-7 cells treated
with isonimesulide and two selected carborane derivatives (4a and 4b). Subsequently,
isonimesulide carborane derivatives induced strong apoptosis which was not mediated by
caspase activation. On the other hand, isonimesulide initiated caspase-mediated apoptosis
and reduced proliferation at a significantly lower rate than its carborane derivatives. In
further investigations, intensive apoptosis manifested with the irregular shape of nuclei,
and chromatin condensation was confirmed by propidium iodide (PI) staining of treated
MCF-7 cells using fluorescent microscopy. Finally, the inhibited production of reactive
oxygen and nitrogen species (ROS/RNS) was observed only in the case of 4b. The new features
of isonimesulide and its carborane derivatives are reflected in their strong antitumor
potential, which opens numerous possibilities for further research.
PB  - Kragujevac: Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine
C3  - Abstract Book: The second Serbian Molecular Medicine Congress; 2023 Oct 6-8; Foča, Bosnia and Herzegovina
T1  - Aнтитуморски потенцијал изонимесулида и његових деривата карборана
T1  - Antitumor potential of isonimesulide and its carborane derivatives
SP  - 85
EP  - 87
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6259
ER  - 

@conference{
author = "Komazec, Teodora and Useini, Liridona and Mijatović, Sanja and Hey-Hawkins, Evamarie and Maksimović-Ivanić, Danijela",
year = "2023",
abstract = "Нестероидни антиинфламаторни лекови (НСАИЛ) у које између осталог
спада нимесулид показали су антитуморски ефекат против различитих типо-
ва туморских ћелијских линија. Потенцијални цитотоксични ефекат изониме-
сулида, члана породице нимесулида, и његових деривата карборана одређен је
на HT29, HCT116, MCF-7, А375 и А549 хуманим ћелијским линијама. Вијабил-
ност свих тестираних ћелијских линија је дозно-зависно смањена, што је по-
казано МТТ и CV тестовима. Селективност ових једињења према туморском
фенотипу је показана на МRC-5 ћелијама и ћелијама перитонеалног ексудата
мишa, под идентичним експерименталним условима. Проточна цитофлуото-
метријска анализа је открила значајно смањење деобног потенцијала МCF-7
ћелија, након третмана изонимесулидом и његовим одабраним дериватима
карборана (4а и 4б). Показано је да су карборански деривати изонимесулида
изазвали снажну апоптозу која није била посредована активацијом каспазе.
Са друге стране, изонимесулид је покренуо апоптозу посредовану активаци-
јом каспаза и смањио пролиферацију знатно нижом стопом од његових кар-
боранскх деривата. У даљем истраживању апоптозу потврђујемо пропидијум
јодид бојењем МCF-7 ћелија применом флуоресцентне микроскопије. Код
третираних ћелија уочавамо интензивну апоптозу која се манифестује непра-
вилним обликом једара и кондензацијом хроматина. Коначно, инхибирана
производња реактивних врста кисеоника и азота примећена је само у случају
деривата 4б. Нове карактеристике изонимесулида и његових деривата карбо-
рана огледају се у њиховом снажном антитуморном потенцијалу, што отвара
бројне могућности за даља истраживања., Nonsteroidal anti-inflammatory drugs (NSAIDs) such as nimesulide have shown
antitumor effects against different types of tumor cell lines. The potential cytotoxic effect
of isonimesulide, a member of the nimesulide family, and its carborane derivatives
was determined against HT29, HCT116, MCF-7, A375, and A549 human cell lines. The
viability of all tested cell lines was dose-dependently decreased as shown by 3-(4,5-dimethythiazol-
2-yl)-2,5-diphenyltetrazolium bromide and crystal violet assays. The selectivity
of these compounds toward a tumor phenotype was demonstrated on MRC-5
and peritoneal exudate cells under identical experimental conditions. Flow cytometric
analysis revealed a significant reduction in the division potential of MCF-7 cells treated
with isonimesulide and two selected carborane derivatives (4a and 4b). Subsequently,
isonimesulide carborane derivatives induced strong apoptosis which was not mediated by
caspase activation. On the other hand, isonimesulide initiated caspase-mediated apoptosis
and reduced proliferation at a significantly lower rate than its carborane derivatives. In
further investigations, intensive apoptosis manifested with the irregular shape of nuclei,
and chromatin condensation was confirmed by propidium iodide (PI) staining of treated
MCF-7 cells using fluorescent microscopy. Finally, the inhibited production of reactive
oxygen and nitrogen species (ROS/RNS) was observed only in the case of 4b. The new features
of isonimesulide and its carborane derivatives are reflected in their strong antitumor
potential, which opens numerous possibilities for further research.",
publisher = "Kragujevac: Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine",
journal = "Abstract Book: The second Serbian Molecular Medicine Congress; 2023 Oct 6-8; Foča, Bosnia and Herzegovina",
title = "Aнтитуморски потенцијал изонимесулида и његових деривата карборана, Antitumor potential of isonimesulide and its carborane derivatives",
pages = "85-87",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6259"
}

Komazec, T., Useini, L., Mijatović, S., Hey-Hawkins, E.,& Maksimović-Ivanić, D.. (2023). Aнтитуморски потенцијал изонимесулида и његових деривата карборана. in Abstract Book: The second Serbian Molecular Medicine Congress; 2023 Oct 6-8; Foča, Bosnia and Herzegovina
Kragujevac: Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine., 85-87.
https://hdl.handle.net/21.15107/rcub_ibiss_6259

Komazec T, Useini L, Mijatović S, Hey-Hawkins E, Maksimović-Ivanić D. Aнтитуморски потенцијал изонимесулида и његових деривата карборана. in Abstract Book: The second Serbian Molecular Medicine Congress; 2023 Oct 6-8; Foča, Bosnia and Herzegovina. 2023;:85-87.
https://hdl.handle.net/21.15107/rcub_ibiss_6259 .

Komazec, Teodora, Useini, Liridona, Mijatović, Sanja, Hey-Hawkins, Evamarie, Maksimović-Ivanić, Danijela, "Aнтитуморски потенцијал изонимесулида и његових деривата карборана" in Abstract Book: The second Serbian Molecular Medicine Congress; 2023 Oct 6-8; Foča, Bosnia and Herzegovina (2023):85-87,
https://hdl.handle.net/21.15107/rcub_ibiss_6259 .

TY  - CONF
AU  - Murganić, Blagoje
AU  - Kazimir, Aleksandar
AU  - Jelača, Sanja
AU  - Tanić, Nikola
AU  - Tanić, Nasta
AU  - Hey-Hawkins, Evamarie
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6244
AB  - Background: Estrogen receptor-positive (ER+) breast cancer accounts for approximately 70% of all cases and, concordantly, anti-estrogen therapies present a leading therapeutic choice. Interestingly, tamoxifen, which is the most commonly used drug, has also been proven effective in hormone-independent forms of breast cancer, suggesting the existence of intracellular off-targets. Frequent acquisition of therapy resistance presents a platform for the design of tamoxifen derivatives with a 2,2’-bipyridine unit enabling the coordination of transition metal moieties, such as copper(II) dichloride. Copper (Cu) is an essential element involved in the regulation of cellular growth and development. Disruption of its delicate homeostasis results in severe toxicity and hard medical conditions. Increased demand of cancer cells for this micronutrient makes it a valuable candidate for drug design in cancer treatment. The mechanism of action of Cu complexes is typically based on their ability to induce deadly oxidative stress. This study evaluated the efficacy of a copper–tamoxifen hybrid drug on a panel of breast cancer cell lines with varying receptor expression status. Material and Methods: The viability of breast adenocarcinoma cell lines MCF-7, MDA-MB-361, MDA-MB-231, 4T1 and glioma U251 was estimated by MTT and CV assays. Flow cytometric analysis of cells stained with annexin V-FITC/propidium iodide, ApoStat, acridine orange, dihydrorhodamine 123 (DHR),  dihydroethidium (DHE) or 4-amino-5-methylamino-2',7'-difluorofluorescein diacetate (DAF) was used to evaluate cell death, caspase activity, autophagy, production of reactive oxygen and nitrogen species (ROS/RNS), respectively. Results: The Cu-tamoxifen hybrid drug displayed substantially higher hormone-receptor (HR) independent cytotoxic activity compared to previously reported metal complexes with a similar tamoxifen vector.  Massive caspase-dependent apoptotic cell death is partially attenuated by an autophagic process that counteracts death signals. In contrast to the platinum analogue, the copper-based tamoxifen derivative reduces ROS/RNS that may be associated with the intracellular accumulation of the reduced form of CuI which is important for cuproptosis. Conclusion: This study demonstrates the potential of the copper–tamoxifen hybrid drug as an intriguing alternative to commonly used platinum complexes in treatment of cancer. Its safety and efficiency will be further estimated in vivo.
PB  - Belgrade: Serbian Association for Cancer Research
C3  - Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia
T1  - Potential of Tamoxifen-based Copper(II) Dichloride in Breast Cancer Therapy
SP  - 95
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6244
ER  - 

@conference{
author = "Murganić, Blagoje and Kazimir, Aleksandar and Jelača, Sanja and Tanić, Nikola and Tanić, Nasta and Hey-Hawkins, Evamarie and Mijatović, Sanja and Maksimović-Ivanić, Danijela",
year = "2023",
abstract = "Background: Estrogen receptor-positive (ER+) breast cancer accounts for approximately 70% of all cases and, concordantly, anti-estrogen therapies present a leading therapeutic choice. Interestingly, tamoxifen, which is the most commonly used drug, has also been proven effective in hormone-independent forms of breast cancer, suggesting the existence of intracellular off-targets. Frequent acquisition of therapy resistance presents a platform for the design of tamoxifen derivatives with a 2,2’-bipyridine unit enabling the coordination of transition metal moieties, such as copper(II) dichloride. Copper (Cu) is an essential element involved in the regulation of cellular growth and development. Disruption of its delicate homeostasis results in severe toxicity and hard medical conditions. Increased demand of cancer cells for this micronutrient makes it a valuable candidate for drug design in cancer treatment. The mechanism of action of Cu complexes is typically based on their ability to induce deadly oxidative stress. This study evaluated the efficacy of a copper–tamoxifen hybrid drug on a panel of breast cancer cell lines with varying receptor expression status. Material and Methods: The viability of breast adenocarcinoma cell lines MCF-7, MDA-MB-361, MDA-MB-231, 4T1 and glioma U251 was estimated by MTT and CV assays. Flow cytometric analysis of cells stained with annexin V-FITC/propidium iodide, ApoStat, acridine orange, dihydrorhodamine 123 (DHR),  dihydroethidium (DHE) or 4-amino-5-methylamino-2',7'-difluorofluorescein diacetate (DAF) was used to evaluate cell death, caspase activity, autophagy, production of reactive oxygen and nitrogen species (ROS/RNS), respectively. Results: The Cu-tamoxifen hybrid drug displayed substantially higher hormone-receptor (HR) independent cytotoxic activity compared to previously reported metal complexes with a similar tamoxifen vector.  Massive caspase-dependent apoptotic cell death is partially attenuated by an autophagic process that counteracts death signals. In contrast to the platinum analogue, the copper-based tamoxifen derivative reduces ROS/RNS that may be associated with the intracellular accumulation of the reduced form of CuI which is important for cuproptosis. Conclusion: This study demonstrates the potential of the copper–tamoxifen hybrid drug as an intriguing alternative to commonly used platinum complexes in treatment of cancer. Its safety and efficiency will be further estimated in vivo.",
publisher = "Belgrade: Serbian Association for Cancer Research",
journal = "Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia",
title = "Potential of Tamoxifen-based Copper(II) Dichloride in Breast Cancer Therapy",
pages = "95",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6244"
}

Murganić, B., Kazimir, A., Jelača, S., Tanić, N., Tanić, N., Hey-Hawkins, E., Mijatović, S.,& Maksimović-Ivanić, D.. (2023). Potential of Tamoxifen-based Copper(II) Dichloride in Breast Cancer Therapy. in Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia
Belgrade: Serbian Association for Cancer Research., 95.
https://hdl.handle.net/21.15107/rcub_ibiss_6244

Murganić B, Kazimir A, Jelača S, Tanić N, Tanić N, Hey-Hawkins E, Mijatović S, Maksimović-Ivanić D. Potential of Tamoxifen-based Copper(II) Dichloride in Breast Cancer Therapy. in Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia. 2023;:95.
https://hdl.handle.net/21.15107/rcub_ibiss_6244 .

Murganić, Blagoje, Kazimir, Aleksandar, Jelača, Sanja, Tanić, Nikola, Tanić, Nasta, Hey-Hawkins, Evamarie, Mijatović, Sanja, Maksimović-Ivanić, Danijela, "Potential of Tamoxifen-based Copper(II) Dichloride in Breast Cancer Therapy" in Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia (2023):95,
https://hdl.handle.net/21.15107/rcub_ibiss_6244 .

TY  - CONF
AU  - Komazec, Teodora
AU  - Mihajlović, Ekatarina
AU  - Bovan, Dijana
AU  - Mijatović, Sanja
AU  - Predarska, Ivana
AU  - Hey-Hawkins, Evamarie
AU  - Kaluđerović, Goran N.
AU  - Maksimović-Ivanić, Danijela
PY  - 2023
UR  - https://www.sdir.ac.rs/oncology-insights/
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6215
AB  - Background: Active contribution of cyclooxygenase enzymes (COX) and their products, in particular prostaglandin E2, to tumor progression makes this enzyme an attractive target for molecular therapy in cancer. The combination of conventional chemotherapeutic drugs with COX1/2 inhibitors, and further enhancement of their delivery into target tissue can be a highly prospective approach in cancer therapy, especially in advanced stages. Accordingly, a cytostatic and anti-inflammatory drug conjugate was synthesised, as well as its immobilization in mesoporous nanostructured silica SBA-15. Detailed evaluation of the cytotoxic potential and the mechanism of action of this conjugate and the appropriate material on B16 cells was further performed in vitro and in vivo. Material and Methods: Cell viability of B16 melanoma cells was determined by MTT and CV assays. Cell morphology was estimated by hematoxylin–eosin and Oil Red O staining using light microscopy, while changes in the nuclei were validated by PI staining using fluorescent microscopy. Differentiation of melanoma cells was determined by measurement of tyrosinase activity and the presence of melanin. Syngeneic C57BL/6 mice model was used for in vivo assessment of the tumorigenic potential of B16 cells exposed to free and SBA-15 loaded conjugate in vitro, as well as for the evaluation of the antitumor potential of the experimental substances given in the therapeutic regimen. Results and Conclusion: Exposure to free or immobilized cisplatin-ibuprofen conjugate decreased the viability of the B16 cell culture while morphology of survived cells was changed. Cytoplasm of enlarged and elongated cells showed intensive granularity with enhanced lipid content and huge irregularly shaped nuclei with prominent heterochromatin foci, all of which indicated senescent state. Increased activity of tyrosinase and the presence of melanin compared to the control, referred to the differentiation of melanoma cells toward primary phenotype. Further inoculation of pretreated B16 cells into C57BL/6 mice showed decreased potential to form tumor in comparison to tumorigenic potential of untreated cells. Additionally, in vivo application of free and SBA-15 immobilized conjugate in therapeutic regiment led to statistically significant reduction of tumor volume, with only fewer signs of toxicity compared to cisplatin as positive control. New knowledge about this compound and corresponding material is reflected in their antitumor potential on mouse melanoma cells, which opens numerous possibilities for further research.
PB  - Belgrade, Serbia: Serbian Associaton for Cancer Research
C3  - Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia
T1  - The effects of cisplatin-ibuprofen conjugate free and immobilized in mesoporous nanostructured silica on the change of morphology of mouse melanoma cells, and antitumor potential in vivo
SP  - 62
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6215
ER  - 

@conference{
author = "Komazec, Teodora and Mihajlović, Ekatarina and Bovan, Dijana and Mijatović, Sanja and Predarska, Ivana and Hey-Hawkins, Evamarie and Kaluđerović, Goran N. and Maksimović-Ivanić, Danijela",
year = "2023",
abstract = "Background: Active contribution of cyclooxygenase enzymes (COX) and their products, in particular prostaglandin E2, to tumor progression makes this enzyme an attractive target for molecular therapy in cancer. The combination of conventional chemotherapeutic drugs with COX1/2 inhibitors, and further enhancement of their delivery into target tissue can be a highly prospective approach in cancer therapy, especially in advanced stages. Accordingly, a cytostatic and anti-inflammatory drug conjugate was synthesised, as well as its immobilization in mesoporous nanostructured silica SBA-15. Detailed evaluation of the cytotoxic potential and the mechanism of action of this conjugate and the appropriate material on B16 cells was further performed in vitro and in vivo. Material and Methods: Cell viability of B16 melanoma cells was determined by MTT and CV assays. Cell morphology was estimated by hematoxylin–eosin and Oil Red O staining using light microscopy, while changes in the nuclei were validated by PI staining using fluorescent microscopy. Differentiation of melanoma cells was determined by measurement of tyrosinase activity and the presence of melanin. Syngeneic C57BL/6 mice model was used for in vivo assessment of the tumorigenic potential of B16 cells exposed to free and SBA-15 loaded conjugate in vitro, as well as for the evaluation of the antitumor potential of the experimental substances given in the therapeutic regimen. Results and Conclusion: Exposure to free or immobilized cisplatin-ibuprofen conjugate decreased the viability of the B16 cell culture while morphology of survived cells was changed. Cytoplasm of enlarged and elongated cells showed intensive granularity with enhanced lipid content and huge irregularly shaped nuclei with prominent heterochromatin foci, all of which indicated senescent state. Increased activity of tyrosinase and the presence of melanin compared to the control, referred to the differentiation of melanoma cells toward primary phenotype. Further inoculation of pretreated B16 cells into C57BL/6 mice showed decreased potential to form tumor in comparison to tumorigenic potential of untreated cells. Additionally, in vivo application of free and SBA-15 immobilized conjugate in therapeutic regiment led to statistically significant reduction of tumor volume, with only fewer signs of toxicity compared to cisplatin as positive control. New knowledge about this compound and corresponding material is reflected in their antitumor potential on mouse melanoma cells, which opens numerous possibilities for further research.",
publisher = "Belgrade, Serbia: Serbian Associaton for Cancer Research",
journal = "Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia",
title = "The effects of cisplatin-ibuprofen conjugate free and immobilized in mesoporous nanostructured silica on the change of morphology of mouse melanoma cells, and antitumor potential in vivo",
pages = "62",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6215"
}

Komazec, T., Mihajlović, E., Bovan, D., Mijatović, S., Predarska, I., Hey-Hawkins, E., Kaluđerović, G. N.,& Maksimović-Ivanić, D.. (2023). The effects of cisplatin-ibuprofen conjugate free and immobilized in mesoporous nanostructured silica on the change of morphology of mouse melanoma cells, and antitumor potential in vivo. in Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia
Belgrade, Serbia: Serbian Associaton for Cancer Research., 62.
https://hdl.handle.net/21.15107/rcub_ibiss_6215

Komazec T, Mihajlović E, Bovan D, Mijatović S, Predarska I, Hey-Hawkins E, Kaluđerović GN, Maksimović-Ivanić D. The effects of cisplatin-ibuprofen conjugate free and immobilized in mesoporous nanostructured silica on the change of morphology of mouse melanoma cells, and antitumor potential in vivo. in Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia. 2023;:62.
https://hdl.handle.net/21.15107/rcub_ibiss_6215 .

Komazec, Teodora, Mihajlović, Ekatarina, Bovan, Dijana, Mijatović, Sanja, Predarska, Ivana, Hey-Hawkins, Evamarie, Kaluđerović, Goran N., Maksimović-Ivanić, Danijela, "The effects of cisplatin-ibuprofen conjugate free and immobilized in mesoporous nanostructured silica on the change of morphology of mouse melanoma cells, and antitumor potential in vivo" in Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia (2023):62,
https://hdl.handle.net/21.15107/rcub_ibiss_6215 .

TY  - CONF
AU  - Komazec, Teodora
AU  - Mihajlović, Ekatarina
AU  - Bovan, Dijana
AU  - Mijatović, Sanja
AU  - Predarska, Ivana
AU  - Kaluđerović, Goran N.
AU  - Hey-Hawkins, Evamarie
AU  - Maksimović-Ivanić, Danijela
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6217
AB  - Overexpression of cyclooxygenase (COX) and thus, prostaglandin E2 in numerous cancers
justified COX inhibitors testing in cancer prevention or treatment 1. Conjugate molecules of
COX inhibitors and common chemotherapeutic drugs, as well as their immobilization in
nanoparticles that increases drug delivery and accumulation in tumor tissue, can potentially
improve approaches in cancer therapy. Cisplatin-naproxen conjugate and corresponding
SBA-15 counterpart decreased the viability of B16 cells. Enlarged and elongated cells with
distinctly granular cytoplasm and the increased presence of lipid droplets were noticed
after haematoxylin–eosin and Oil Red O staining of treated cultures. In addition, enormous
nuclei and markedly heterochromatin foci were confirmed by PI staining indicating
establishment of senescent state upon the treatment. Alongside, differentiation of
melanoma cells toward melanocytes was demonstrated by elevated tyrosinase activity and
presence of melanin, thus leading to reduced tumorigenic potential in vivo. In addition,
cisplatin-naproxen conjugate and corresponding SBA-15 counterpart significantly reduced
melanoma growth in C57BL/6 mice, with lesser signs of toxicity compared to cisplatin as
a positive control. Strong antitumor potential of both, free and immobilized conjugates on
mouse melanoma cells opens numerous possibilities for further research.
PB  - Belgrade: Faculty of Chemistry
C3  - Biochemistry in Biotechnology: Serbian Biochemical Society, Twelfth Conference, International scientific meeting; 2023 Sep 21-23; Belgrade, Serbia
T1  - Cisplatin-naproxen conjugate free and loaded in SBA- 15 indicate morphological changes and antitumor activity in vivo in mouse melanoma model
SP  - 97
EP  - 98
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6217
ER  - 

@conference{
author = "Komazec, Teodora and Mihajlović, Ekatarina and Bovan, Dijana and Mijatović, Sanja and Predarska, Ivana and Kaluđerović, Goran N. and Hey-Hawkins, Evamarie and Maksimović-Ivanić, Danijela",
year = "2023",
abstract = "Overexpression of cyclooxygenase (COX) and thus, prostaglandin E2 in numerous cancers
justified COX inhibitors testing in cancer prevention or treatment 1. Conjugate molecules of
COX inhibitors and common chemotherapeutic drugs, as well as their immobilization in
nanoparticles that increases drug delivery and accumulation in tumor tissue, can potentially
improve approaches in cancer therapy. Cisplatin-naproxen conjugate and corresponding
SBA-15 counterpart decreased the viability of B16 cells. Enlarged and elongated cells with
distinctly granular cytoplasm and the increased presence of lipid droplets were noticed
after haematoxylin–eosin and Oil Red O staining of treated cultures. In addition, enormous
nuclei and markedly heterochromatin foci were confirmed by PI staining indicating
establishment of senescent state upon the treatment. Alongside, differentiation of
melanoma cells toward melanocytes was demonstrated by elevated tyrosinase activity and
presence of melanin, thus leading to reduced tumorigenic potential in vivo. In addition,
cisplatin-naproxen conjugate and corresponding SBA-15 counterpart significantly reduced
melanoma growth in C57BL/6 mice, with lesser signs of toxicity compared to cisplatin as
a positive control. Strong antitumor potential of both, free and immobilized conjugates on
mouse melanoma cells opens numerous possibilities for further research.",
publisher = "Belgrade: Faculty of Chemistry",
journal = "Biochemistry in Biotechnology: Serbian Biochemical Society, Twelfth Conference, International scientific meeting; 2023 Sep 21-23; Belgrade, Serbia",
title = "Cisplatin-naproxen conjugate free and loaded in SBA- 15 indicate morphological changes and antitumor activity in vivo in mouse melanoma model",
pages = "97-98",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6217"
}

Komazec, T., Mihajlović, E., Bovan, D., Mijatović, S., Predarska, I., Kaluđerović, G. N., Hey-Hawkins, E.,& Maksimović-Ivanić, D.. (2023). Cisplatin-naproxen conjugate free and loaded in SBA- 15 indicate morphological changes and antitumor activity in vivo in mouse melanoma model. in Biochemistry in Biotechnology: Serbian Biochemical Society, Twelfth Conference, International scientific meeting; 2023 Sep 21-23; Belgrade, Serbia
Belgrade: Faculty of Chemistry., 97-98.
https://hdl.handle.net/21.15107/rcub_ibiss_6217

Komazec T, Mihajlović E, Bovan D, Mijatović S, Predarska I, Kaluđerović GN, Hey-Hawkins E, Maksimović-Ivanić D. Cisplatin-naproxen conjugate free and loaded in SBA- 15 indicate morphological changes and antitumor activity in vivo in mouse melanoma model. in Biochemistry in Biotechnology: Serbian Biochemical Society, Twelfth Conference, International scientific meeting; 2023 Sep 21-23; Belgrade, Serbia. 2023;:97-98.
https://hdl.handle.net/21.15107/rcub_ibiss_6217 .

Komazec, Teodora, Mihajlović, Ekatarina, Bovan, Dijana, Mijatović, Sanja, Predarska, Ivana, Kaluđerović, Goran N., Hey-Hawkins, Evamarie, Maksimović-Ivanić, Danijela, "Cisplatin-naproxen conjugate free and loaded in SBA- 15 indicate morphological changes and antitumor activity in vivo in mouse melanoma model" in Biochemistry in Biotechnology: Serbian Biochemical Society, Twelfth Conference, International scientific meeting; 2023 Sep 21-23; Belgrade, Serbia (2023):97-98,
https://hdl.handle.net/21.15107/rcub_ibiss_6217 .

TY  - JOUR
AU  - Braun, Sebastian
AU  - Jelača, Sanja
AU  - Laube, Marcus
AU  - George, Sven
AU  - Hofmann, Bettina
AU  - Lönnecke, Peter
AU  - Steinhilber, Dieter
AU  - Pietzsch, Jens
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Hey-Hawkins, Evamarie
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5823
AB  - Targeting inflammatory mediators and related signaling pathways may offer a rational strategy for the treatment of cancer. The incorporation of metabolically stable, sterically demanding, and hydrophobic carboranes in dual cycloxygenase-2 (COX-2)/5-lipoxygenase (5-LO) inhibitors that are key enzymes in the biosynthesis of eicosanoids is a promising approach. The di-tert-butylphenol derivatives R-830, S-2474, KME-4, and E-5110 represent potent dual COX-2/5-LO inhibitors. The incorporation of p-carborane and further substitution of the p-position resulted in four carborane-based di-tert-butylphenol analogs that showed no or weak COX inhibition but high 5-LO inhibitory activities in vitro. Cell viability studies on five human cancer cell lines revealed that the p-carborane analogs R-830-Cb, S-2474-Cb, KME-4-Cb, and E-5110-Cb exhibited lower anticancer activity compared to the related di-tert-butylphenols. Interestingly, R-830-Cb did not affect the viability of primary cells and suppressed HCT116 cell proliferation more potently than its carbon-based R-830 counterpart. Considering all the advantages of boron cluster incorporation for enhancement of drug biostability, selectivity, and availability of drugs, R-830-Cb can be tested in further mechanistic and in vivo studies.
PB  - Basel: MDPI
T2  - Molecules
T1  - Synthesis and In Vitro Biological Evaluation of p-Carborane-Based Di-tert-butylphenol Analogs
IS  - 11
VL  - 28
DO  - 10.3390/molecules28114547
SP  - 4547
ER  - 

@article{
author = "Braun, Sebastian and Jelača, Sanja and Laube, Marcus and George, Sven and Hofmann, Bettina and Lönnecke, Peter and Steinhilber, Dieter and Pietzsch, Jens and Mijatović, Sanja and Maksimović-Ivanić, Danijela and Hey-Hawkins, Evamarie",
year = "2023",
abstract = "Targeting inflammatory mediators and related signaling pathways may offer a rational strategy for the treatment of cancer. The incorporation of metabolically stable, sterically demanding, and hydrophobic carboranes in dual cycloxygenase-2 (COX-2)/5-lipoxygenase (5-LO) inhibitors that are key enzymes in the biosynthesis of eicosanoids is a promising approach. The di-tert-butylphenol derivatives R-830, S-2474, KME-4, and E-5110 represent potent dual COX-2/5-LO inhibitors. The incorporation of p-carborane and further substitution of the p-position resulted in four carborane-based di-tert-butylphenol analogs that showed no or weak COX inhibition but high 5-LO inhibitory activities in vitro. Cell viability studies on five human cancer cell lines revealed that the p-carborane analogs R-830-Cb, S-2474-Cb, KME-4-Cb, and E-5110-Cb exhibited lower anticancer activity compared to the related di-tert-butylphenols. Interestingly, R-830-Cb did not affect the viability of primary cells and suppressed HCT116 cell proliferation more potently than its carbon-based R-830 counterpart. Considering all the advantages of boron cluster incorporation for enhancement of drug biostability, selectivity, and availability of drugs, R-830-Cb can be tested in further mechanistic and in vivo studies.",
publisher = "Basel: MDPI",
journal = "Molecules",
title = "Synthesis and In Vitro Biological Evaluation of p-Carborane-Based Di-tert-butylphenol Analogs",
number = "11",
volume = "28",
doi = "10.3390/molecules28114547",
pages = "4547"
}

Braun, S., Jelača, S., Laube, M., George, S., Hofmann, B., Lönnecke, P., Steinhilber, D., Pietzsch, J., Mijatović, S., Maksimović-Ivanić, D.,& Hey-Hawkins, E.. (2023). Synthesis and In Vitro Biological Evaluation of p-Carborane-Based Di-tert-butylphenol Analogs. in Molecules
Basel: MDPI., 28(11), 4547.
https://doi.org/10.3390/molecules28114547

Braun S, Jelača S, Laube M, George S, Hofmann B, Lönnecke P, Steinhilber D, Pietzsch J, Mijatović S, Maksimović-Ivanić D, Hey-Hawkins E. Synthesis and In Vitro Biological Evaluation of p-Carborane-Based Di-tert-butylphenol Analogs. in Molecules. 2023;28(11):4547.
doi:10.3390/molecules28114547 .

Braun, Sebastian, Jelača, Sanja, Laube, Marcus, George, Sven, Hofmann, Bettina, Lönnecke, Peter, Steinhilber, Dieter, Pietzsch, Jens, Mijatović, Sanja, Maksimović-Ivanić, Danijela, Hey-Hawkins, Evamarie, "Synthesis and In Vitro Biological Evaluation of p-Carborane-Based Di-tert-butylphenol Analogs" in Molecules, 28, no. 11 (2023):4547,
https://doi.org/10.3390/molecules28114547 . .

TY  - JOUR
AU  - Useini, Liridona
AU  - Komazec, Teodora
AU  - Laube, Markus
AU  - Lönnecke, Peter
AU  - Schädlich, Jonas
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Pietzsch, Jens
AU  - Hey-Hawkins, Evamarie
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5826
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most widely used
therapeutics against pain, fever, and inflammation; additionally, antitumor
properties are reported. NSAIDs reduce the synthesis of prostaglandins by
inhibiting the cyclooxygenase (COX) isoforms COX-1 and COX-2. As
nonselective inhibition is associated with off-target effects, strategies to
achieve selectivity for the clinically preferred isoform COX-2 are of high
interest. The modification of NSAIDs using carborane clusters as phenyl
mimetics is reported to alter the selectivity profile through size exclusion.
Inspired by these findings, isonimesulide and its carborane derivatives are
prepared. The biological screening shows that the carborane containing
compounds exhibit a stronger antitumor potential compared to nimesulide
and isonimesulide. Furthermore, the replacement of the phenyl ring of
isonimesulide with a carborane moiety resulted in a shift of the COX activity
from nonactive to COX-active compounds.
PB  - Hoboken: Wiley
T2  - Advanced Therapeutics
T1  - Isonimesulide and Its Carborane Analogues as Isoform-Selective COX Inhibitors and Antitumor Agents
DO  - 10.1002/adtp.202300117
SP  - 2300117
ER  - 

@article{
author = "Useini, Liridona and Komazec, Teodora and Laube, Markus and Lönnecke, Peter and Schädlich, Jonas and Mijatović, Sanja and Maksimović-Ivanić, Danijela and Pietzsch, Jens and Hey-Hawkins, Evamarie",
year = "2023",
abstract = "Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most widely used
therapeutics against pain, fever, and inflammation; additionally, antitumor
properties are reported. NSAIDs reduce the synthesis of prostaglandins by
inhibiting the cyclooxygenase (COX) isoforms COX-1 and COX-2. As
nonselective inhibition is associated with off-target effects, strategies to
achieve selectivity for the clinically preferred isoform COX-2 are of high
interest. The modification of NSAIDs using carborane clusters as phenyl
mimetics is reported to alter the selectivity profile through size exclusion.
Inspired by these findings, isonimesulide and its carborane derivatives are
prepared. The biological screening shows that the carborane containing
compounds exhibit a stronger antitumor potential compared to nimesulide
and isonimesulide. Furthermore, the replacement of the phenyl ring of
isonimesulide with a carborane moiety resulted in a shift of the COX activity
from nonactive to COX-active compounds.",
publisher = "Hoboken: Wiley",
journal = "Advanced Therapeutics",
title = "Isonimesulide and Its Carborane Analogues as Isoform-Selective COX Inhibitors and Antitumor Agents",
doi = "10.1002/adtp.202300117",
pages = "2300117"
}

Useini, L., Komazec, T., Laube, M., Lönnecke, P., Schädlich, J., Mijatović, S., Maksimović-Ivanić, D., Pietzsch, J.,& Hey-Hawkins, E.. (2023). Isonimesulide and Its Carborane Analogues as Isoform-Selective COX Inhibitors and Antitumor Agents. in Advanced Therapeutics
Hoboken: Wiley., 2300117.
https://doi.org/10.1002/adtp.202300117

Useini L, Komazec T, Laube M, Lönnecke P, Schädlich J, Mijatović S, Maksimović-Ivanić D, Pietzsch J, Hey-Hawkins E. Isonimesulide and Its Carborane Analogues as Isoform-Selective COX Inhibitors and Antitumor Agents. in Advanced Therapeutics. 2023;:2300117.
doi:10.1002/adtp.202300117 .

Useini, Liridona, Komazec, Teodora, Laube, Markus, Lönnecke, Peter, Schädlich, Jonas, Mijatović, Sanja, Maksimović-Ivanić, Danijela, Pietzsch, Jens, Hey-Hawkins, Evamarie, "Isonimesulide and Its Carborane Analogues as Isoform-Selective COX Inhibitors and Antitumor Agents" in Advanced Therapeutics (2023):2300117,
https://doi.org/10.1002/adtp.202300117 . .

TY  - JOUR
AU  - Useini, Liridona
AU  - Mojić, Marija
AU  - Laube, Markus
AU  - Lönnecke, Peter
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Pietzsch, Jens
AU  - Hey‐Hawkins, Evamarie
PY  - 2023
UR  - https://onlinelibrary.wiley.com/doi/10.1002/cmdc.202200583
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5432
AB  - Fenoprofen is a widely used nonsteroidal anti-inflammatory drug (NSAID) against rheumatoid arthritis, degenerative joint disease, ankylosing spondylitis and gout. Like other NSAIDs, fenoprofen inhibits the synthesis of prostaglandins by blocking both cyclooxygenase (COX) isoforms, COX-1 the “house-keeping” enzyme and COX-2 the induced isoform from pathological stimuli. Unselective inhibition of both COX isoforms results in many side effects, but off-target effects have also been reported. The steric modifications of the drugs could afford the desired COX-2 selectivity. Furthermore, NSAIDs have shown promising cytotoxic properties. The structural modification of fenoprofen using bulky dicarba-closo-dodecaborane(12) (carborane) clusters and the biological evaluation of the carborane analogues for COX inhibition and antitumor potential showed that the carborane analogues exhibit stronger antitumor potential compared to their respective aryl-based compounds.
PB  - John Wiley and Sons Ltd
T2  - ChemMedChem
T1  - Carborane Analogues of Fenoprofen Exhibit Improved Antitumor Activity
IS  - 5
VL  - 18
DO  - 10.1002/cmdc.202200583
SP  - e202200583
ER  - 

@article{
author = "Useini, Liridona and Mojić, Marija and Laube, Markus and Lönnecke, Peter and Mijatović, Sanja and Maksimović-Ivanić, Danijela and Pietzsch, Jens and Hey‐Hawkins, Evamarie",
year = "2023",
abstract = "Fenoprofen is a widely used nonsteroidal anti-inflammatory drug (NSAID) against rheumatoid arthritis, degenerative joint disease, ankylosing spondylitis and gout. Like other NSAIDs, fenoprofen inhibits the synthesis of prostaglandins by blocking both cyclooxygenase (COX) isoforms, COX-1 the “house-keeping” enzyme and COX-2 the induced isoform from pathological stimuli. Unselective inhibition of both COX isoforms results in many side effects, but off-target effects have also been reported. The steric modifications of the drugs could afford the desired COX-2 selectivity. Furthermore, NSAIDs have shown promising cytotoxic properties. The structural modification of fenoprofen using bulky dicarba-closo-dodecaborane(12) (carborane) clusters and the biological evaluation of the carborane analogues for COX inhibition and antitumor potential showed that the carborane analogues exhibit stronger antitumor potential compared to their respective aryl-based compounds.",
publisher = "John Wiley and Sons Ltd",
journal = "ChemMedChem",
title = "Carborane Analogues of Fenoprofen Exhibit Improved Antitumor Activity",
number = "5",
volume = "18",
doi = "10.1002/cmdc.202200583",
pages = "e202200583"
}

Useini, L., Mojić, M., Laube, M., Lönnecke, P., Mijatović, S., Maksimović-Ivanić, D., Pietzsch, J.,& Hey‐Hawkins, E.. (2023). Carborane Analogues of Fenoprofen Exhibit Improved Antitumor Activity. in ChemMedChem
John Wiley and Sons Ltd., 18(5), e202200583.
https://doi.org/10.1002/cmdc.202200583

Useini L, Mojić M, Laube M, Lönnecke P, Mijatović S, Maksimović-Ivanić D, Pietzsch J, Hey‐Hawkins E. Carborane Analogues of Fenoprofen Exhibit Improved Antitumor Activity. in ChemMedChem. 2023;18(5):e202200583.
doi:10.1002/cmdc.202200583 .

Useini, Liridona, Mojić, Marija, Laube, Markus, Lönnecke, Peter, Mijatović, Sanja, Maksimović-Ivanić, Danijela, Pietzsch, Jens, Hey‐Hawkins, Evamarie, "Carborane Analogues of Fenoprofen Exhibit Improved Antitumor Activity" in ChemMedChem, 18, no. 5 (2023):e202200583,
https://doi.org/10.1002/cmdc.202200583 . .

TY  - JOUR
AU  - Kazimir, Aleksandr
AU  - Schwarze, Benedikt
AU  - Lönnecke, Peter
AU  - Jelača, Sanja
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Hey-Hawkins, Evamarie
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5469
AB  - The luminal A-subtype of breast cancer, where the oestrogen receptor α (ERα) is overexpressed, is the most frequent one. The prodrug tamoxifen (1) is the clinically used agent, inhibiting the ERα activity via the formation of several active metabolites, such as 4-hydroxytamoxifen (2) or 4,4′-dihydroxytamoxifen (3). In this study, we present the tamoxifen derivative 4-[1,1-bis(4-methoxyphenyl)but-1-en-2-yl]-2,2′-bipyridine (4), which was combined with platinum or palladium dichloride, the former a well-known scaffold in anticancer treatment, to give [PtCl2(4-κ2N,N′)] (5) or [PdCl2(4-κ2N,N′] (6). To prevent fast exchange of weakly coordinating chlorido ligands in aqueous solution, a bulky, highly stable and hydrophobic nido-carborate(−2) ([C2B9H11]2−) was incorporated. The resulting complexes [3-(4-κ2N,N′)-3,1,2-PtC2B9H11] (7) and [3-(4-κ2N,N′)-3,1,2-PdC2B9H11] (8) exhibit a dramatic change in electronic and biological properties compared to 5 and 6. Thus, 8 is highly selective for triple-negative MDA-MB-231 cells (IC50 = 3.7 μM, MTT test), while 7 is completely inactive against this cell line. The observed cytotoxicity of compounds 4–6 and 8 against this triple-negative cell line suggests off-target mechanisms rather than only ERα inhibition, for which these compounds were originally designed. Spectroscopic properties and electronic structures of the metal complexes were investigated for possible explanations of the biological activities.
PB  - Basel: MDPI
T2  - Pharmaceutics
T1  - Metallodrugs against Breast Cancer: Combining the Tamoxifen Vector with Platinum(II) and Palladium(II) Complexes
IS  - 2
VL  - 15
DO  - 10.3390/pharmaceutics15020682
SP  - 682
ER  - 

@article{
author = "Kazimir, Aleksandr and Schwarze, Benedikt and Lönnecke, Peter and Jelača, Sanja and Mijatović, Sanja and Maksimović-Ivanić, Danijela and Hey-Hawkins, Evamarie",
year = "2023",
abstract = "The luminal A-subtype of breast cancer, where the oestrogen receptor α (ERα) is overexpressed, is the most frequent one. The prodrug tamoxifen (1) is the clinically used agent, inhibiting the ERα activity via the formation of several active metabolites, such as 4-hydroxytamoxifen (2) or 4,4′-dihydroxytamoxifen (3). In this study, we present the tamoxifen derivative 4-[1,1-bis(4-methoxyphenyl)but-1-en-2-yl]-2,2′-bipyridine (4), which was combined with platinum or palladium dichloride, the former a well-known scaffold in anticancer treatment, to give [PtCl2(4-κ2N,N′)] (5) or [PdCl2(4-κ2N,N′] (6). To prevent fast exchange of weakly coordinating chlorido ligands in aqueous solution, a bulky, highly stable and hydrophobic nido-carborate(−2) ([C2B9H11]2−) was incorporated. The resulting complexes [3-(4-κ2N,N′)-3,1,2-PtC2B9H11] (7) and [3-(4-κ2N,N′)-3,1,2-PdC2B9H11] (8) exhibit a dramatic change in electronic and biological properties compared to 5 and 6. Thus, 8 is highly selective for triple-negative MDA-MB-231 cells (IC50 = 3.7 μM, MTT test), while 7 is completely inactive against this cell line. The observed cytotoxicity of compounds 4–6 and 8 against this triple-negative cell line suggests off-target mechanisms rather than only ERα inhibition, for which these compounds were originally designed. Spectroscopic properties and electronic structures of the metal complexes were investigated for possible explanations of the biological activities.",
publisher = "Basel: MDPI",
journal = "Pharmaceutics",
title = "Metallodrugs against Breast Cancer: Combining the Tamoxifen Vector with Platinum(II) and Palladium(II) Complexes",
number = "2",
volume = "15",
doi = "10.3390/pharmaceutics15020682",
pages = "682"
}

Kazimir, A., Schwarze, B., Lönnecke, P., Jelača, S., Mijatović, S., Maksimović-Ivanić, D.,& Hey-Hawkins, E.. (2023). Metallodrugs against Breast Cancer: Combining the Tamoxifen Vector with Platinum(II) and Palladium(II) Complexes. in Pharmaceutics
Basel: MDPI., 15(2), 682.
https://doi.org/10.3390/pharmaceutics15020682

Kazimir A, Schwarze B, Lönnecke P, Jelača S, Mijatović S, Maksimović-Ivanić D, Hey-Hawkins E. Metallodrugs against Breast Cancer: Combining the Tamoxifen Vector with Platinum(II) and Palladium(II) Complexes. in Pharmaceutics. 2023;15(2):682.
doi:10.3390/pharmaceutics15020682 .

Kazimir, Aleksandr, Schwarze, Benedikt, Lönnecke, Peter, Jelača, Sanja, Mijatović, Sanja, Maksimović-Ivanić, Danijela, Hey-Hawkins, Evamarie, "Metallodrugs against Breast Cancer: Combining the Tamoxifen Vector with Platinum(II) and Palladium(II) Complexes" in Pharmaceutics, 15, no. 2 (2023):682,
https://doi.org/10.3390/pharmaceutics15020682 . .

TY  - JOUR
AU  - Stockmann, Philipp
AU  - Kuhnert, Lydia
AU  - Leinung, Wencke
AU  - Lakoma, Cathleen
AU  - Scholz, Birte
AU  - Paskaš, Svetlana
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Honscha, Walther
AU  - Hey-Hawkins, Evamarie
PY  - 2023
UR  - https://www.mdpi.com/1999-4923/15/1/241
UR  - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC9866861
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5434
AB  - The ineffectiveness and failing of chemotherapeutic treatments are often associated with multidrug resistance (MDR). MDR is primarily linked to the overexpression of ATP-binding cassette (ABC) transporter proteins in cancer cells. ABCG2 (ATP-binding cassette subfamily G member 2, also known as the breast cancer resistance protein (BCRP)) mediates MDR by an increased drug efflux from the cancer cells. Therefore, the inhibition of ABCG2 activity during chemotherapy ought to improve the efficacy of the administered anti-cancer agents by reversing MDR or by enhancing the agents' pharmacokinetic properties. Significant efforts have been made to develop novel, powerful, selective, and non-toxic inhibitors of BCRP. However, thus far the clinical relevance of BCRP-selective MDR-reversal has been unsuccessful, due to either adverse drug reactions or significant toxicities in vivo. We here report a facile access towards carboranyl quinazoline-based inhibitors of ABCG2. We determined the influence of different methoxy-substitution patterns on the 2-phenylquinazoline scaffold in combination with the beneficial properties of an incorporated inorganic carborane moiety. A series of eight compounds was synthesized and their inhibitory effect on the ABCG2-mediated Hoechst transport was evaluated. Molecular docking studies were performed to better understand the structure-protein interactions of the novel inhibitors, exhibiting putative binding modes within the inner binding site. Further, the most potent, non-toxic compounds were investigated for their potential to reverse ABCG2-mediated mitoxantrone (MXN) resistance. Of these five evaluated compounds, N-(closo-1,7-dicarbadodecaboran(12)-9-yl)-6,7-dimethoxy-2-(3,4,5-trimethoxyphenyl)-quinazolin-4-amine (DMQCd) exhibited the strongest inhibitory effect towards ABCG2 in the lower nanomolar ranges. Additionally, DMQCd was able to reverse BCRP-mediated MDR, making it a promising candidate for further research on hybrid inorganic-organic compounds.
PB  - Basel: MDPI
T2  - Pharmaceutics
T1  - The More the Better-Investigation of Polymethoxylated N-Carboranyl Quinazolines as Novel Hybrid Breast Cancer Resistance Protein Inhibitors
IS  - 1
VL  - 15
DO  - 10.3390/pharmaceutics15010241
SP  - 241
ER  - 

@article{
author = "Stockmann, Philipp and Kuhnert, Lydia and Leinung, Wencke and Lakoma, Cathleen and Scholz, Birte and Paskaš, Svetlana and Mijatović, Sanja and Maksimović-Ivanić, Danijela and Honscha, Walther and Hey-Hawkins, Evamarie",
year = "2023",
abstract = "The ineffectiveness and failing of chemotherapeutic treatments are often associated with multidrug resistance (MDR). MDR is primarily linked to the overexpression of ATP-binding cassette (ABC) transporter proteins in cancer cells. ABCG2 (ATP-binding cassette subfamily G member 2, also known as the breast cancer resistance protein (BCRP)) mediates MDR by an increased drug efflux from the cancer cells. Therefore, the inhibition of ABCG2 activity during chemotherapy ought to improve the efficacy of the administered anti-cancer agents by reversing MDR or by enhancing the agents' pharmacokinetic properties. Significant efforts have been made to develop novel, powerful, selective, and non-toxic inhibitors of BCRP. However, thus far the clinical relevance of BCRP-selective MDR-reversal has been unsuccessful, due to either adverse drug reactions or significant toxicities in vivo. We here report a facile access towards carboranyl quinazoline-based inhibitors of ABCG2. We determined the influence of different methoxy-substitution patterns on the 2-phenylquinazoline scaffold in combination with the beneficial properties of an incorporated inorganic carborane moiety. A series of eight compounds was synthesized and their inhibitory effect on the ABCG2-mediated Hoechst transport was evaluated. Molecular docking studies were performed to better understand the structure-protein interactions of the novel inhibitors, exhibiting putative binding modes within the inner binding site. Further, the most potent, non-toxic compounds were investigated for their potential to reverse ABCG2-mediated mitoxantrone (MXN) resistance. Of these five evaluated compounds, N-(closo-1,7-dicarbadodecaboran(12)-9-yl)-6,7-dimethoxy-2-(3,4,5-trimethoxyphenyl)-quinazolin-4-amine (DMQCd) exhibited the strongest inhibitory effect towards ABCG2 in the lower nanomolar ranges. Additionally, DMQCd was able to reverse BCRP-mediated MDR, making it a promising candidate for further research on hybrid inorganic-organic compounds.",
publisher = "Basel: MDPI",
journal = "Pharmaceutics",
title = "The More the Better-Investigation of Polymethoxylated N-Carboranyl Quinazolines as Novel Hybrid Breast Cancer Resistance Protein Inhibitors",
number = "1",
volume = "15",
doi = "10.3390/pharmaceutics15010241",
pages = "241"
}

Stockmann, P., Kuhnert, L., Leinung, W., Lakoma, C., Scholz, B., Paskaš, S., Mijatović, S., Maksimović-Ivanić, D., Honscha, W.,& Hey-Hawkins, E.. (2023). The More the Better-Investigation of Polymethoxylated N-Carboranyl Quinazolines as Novel Hybrid Breast Cancer Resistance Protein Inhibitors. in Pharmaceutics
Basel: MDPI., 15(1), 241.
https://doi.org/10.3390/pharmaceutics15010241

Stockmann P, Kuhnert L, Leinung W, Lakoma C, Scholz B, Paskaš S, Mijatović S, Maksimović-Ivanić D, Honscha W, Hey-Hawkins E. The More the Better-Investigation of Polymethoxylated N-Carboranyl Quinazolines as Novel Hybrid Breast Cancer Resistance Protein Inhibitors. in Pharmaceutics. 2023;15(1):241.
doi:10.3390/pharmaceutics15010241 .

Stockmann, Philipp, Kuhnert, Lydia, Leinung, Wencke, Lakoma, Cathleen, Scholz, Birte, Paskaš, Svetlana, Mijatović, Sanja, Maksimović-Ivanić, Danijela, Honscha, Walther, Hey-Hawkins, Evamarie, "The More the Better-Investigation of Polymethoxylated N-Carboranyl Quinazolines as Novel Hybrid Breast Cancer Resistance Protein Inhibitors" in Pharmaceutics, 15, no. 1 (2023):241,
https://doi.org/10.3390/pharmaceutics15010241 . .

TY  - JOUR
AU  - Braun, Sebastian
AU  - Paskaš, Svetlana
AU  - Laube, Markus
AU  - George, Sven
AU  - Hofmann, Bettina
AU  - Lönnecke, Peter
AU  - Steinhilber, Dieter
AU  - Pietzsch, Jens
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Hey‐Hawkins, Evamarie
PY  - 2023
UR  - https://onlinelibrary.wiley.com/doi/10.1002/adtp.202200252
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5384
AB  - The selective inhibition of enzymes that catalyze the conversion of arachidonic acid to inflammatory eicosanoids represents a promising approach for cancer therapy. This study, therefore, focuses on the incorporation of metabolically stable, sterically demanding, and hydrophobic carboranes into existing dual cycloxygenase-2 (COX-2)/5-lipoxygenase (5-LO) inhibitors that are key enzymes in the biosynthesis of eicosanoids. Here, the first carborane-containing dual COX-2/5-LO inhibitors derived from RWJ-63556 are presented. The replacement of the fluorophenyl moiety by meta- or para-carborane resulted in five carborane-containing derivatives 3, 6, 9, 13, and 17 that show high inhibitory activities toward COX-2 and 5-LO in vitro. Cell viability studies on the A375 melanoma cell line revealed that meta-carborane derivative 3 shows higher anticancer activity compared to RWJ-63556 based on accumulation of lipid droplets in the cells due to blockage of the COX-2 and 5-LO pathways, indicating a promising approach for the design of potent dual COX-2/5-LO inhibitors.
T2  - Advanced Therapeutics
T1  - In Vitro Cytostatic Effect on Tumor Cells by Carborane‐Based Dual Cyclooxygenase‐2 and 5‐Lipoxygenase Inhibitors
DO  - 10.1002/adtp.202200252
SP  - 2200252
ER  - 

@article{
author = "Braun, Sebastian and Paskaš, Svetlana and Laube, Markus and George, Sven and Hofmann, Bettina and Lönnecke, Peter and Steinhilber, Dieter and Pietzsch, Jens and Mijatović, Sanja and Maksimović-Ivanić, Danijela and Hey‐Hawkins, Evamarie",
year = "2023",
abstract = "The selective inhibition of enzymes that catalyze the conversion of arachidonic acid to inflammatory eicosanoids represents a promising approach for cancer therapy. This study, therefore, focuses on the incorporation of metabolically stable, sterically demanding, and hydrophobic carboranes into existing dual cycloxygenase-2 (COX-2)/5-lipoxygenase (5-LO) inhibitors that are key enzymes in the biosynthesis of eicosanoids. Here, the first carborane-containing dual COX-2/5-LO inhibitors derived from RWJ-63556 are presented. The replacement of the fluorophenyl moiety by meta- or para-carborane resulted in five carborane-containing derivatives 3, 6, 9, 13, and 17 that show high inhibitory activities toward COX-2 and 5-LO in vitro. Cell viability studies on the A375 melanoma cell line revealed that meta-carborane derivative 3 shows higher anticancer activity compared to RWJ-63556 based on accumulation of lipid droplets in the cells due to blockage of the COX-2 and 5-LO pathways, indicating a promising approach for the design of potent dual COX-2/5-LO inhibitors.",
journal = "Advanced Therapeutics",
title = "In Vitro Cytostatic Effect on Tumor Cells by Carborane‐Based Dual Cyclooxygenase‐2 and 5‐Lipoxygenase Inhibitors",
doi = "10.1002/adtp.202200252",
pages = "2200252"
}

Braun, S., Paskaš, S., Laube, M., George, S., Hofmann, B., Lönnecke, P., Steinhilber, D., Pietzsch, J., Mijatović, S., Maksimović-Ivanić, D.,& Hey‐Hawkins, E.. (2023). In Vitro Cytostatic Effect on Tumor Cells by Carborane‐Based Dual Cyclooxygenase‐2 and 5‐Lipoxygenase Inhibitors. in Advanced Therapeutics, 2200252.
https://doi.org/10.1002/adtp.202200252

Braun S, Paskaš S, Laube M, George S, Hofmann B, Lönnecke P, Steinhilber D, Pietzsch J, Mijatović S, Maksimović-Ivanić D, Hey‐Hawkins E. In Vitro Cytostatic Effect on Tumor Cells by Carborane‐Based Dual Cyclooxygenase‐2 and 5‐Lipoxygenase Inhibitors. in Advanced Therapeutics. 2023;:2200252.
doi:10.1002/adtp.202200252 .

Braun, Sebastian, Paskaš, Svetlana, Laube, Markus, George, Sven, Hofmann, Bettina, Lönnecke, Peter, Steinhilber, Dieter, Pietzsch, Jens, Mijatović, Sanja, Maksimović-Ivanić, Danijela, Hey‐Hawkins, Evamarie, "In Vitro Cytostatic Effect on Tumor Cells by Carborane‐Based Dual Cyclooxygenase‐2 and 5‐Lipoxygenase Inhibitors" in Advanced Therapeutics (2023):2200252,
https://doi.org/10.1002/adtp.202200252 . .

TY  - JOUR
AU  - Predarska, Ivana
AU  - Saoud, Mohamad
AU  - Drača, Dijana
AU  - Morgan, Ibrahim
AU  - Komazec, Teodora
AU  - Eichhorn, Thomas
AU  - Mihajlović, Ekatarina
AU  - Dunđerović, Duško
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Hey-Hawkins, Evamarie
AU  - Kaluđerović, Goran N.
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5238
AB  - The main reasons for the limited clinical efficacy of the platinum(II)-based agent cisplatin
include drug resistance and significant side effects. Due to their better stability, as well as the
possibility to introduce biologically active ligands in their axial positions constructing multifunctional
prodrugs, creating platinum(IV) complexes is a tempting strategy for addressing these limitations.
Another strategy for developing chemotherapeutics with lower toxicity relies on the ability of
nanoparticles to accumulate in greater quantities in tumor tissues through passive targeting. To
combine the two approaches, three platinum(IV) conjugates based on a cisplatin scaffold containing
in the axial positions derivatives of caffeic and ferulic acid were prepared and loaded into SBA-
15 to produce the corresponding mesoporous silica nanoparticles (MSNs). The free platinum(IV)
conjugates demonstrated higher or comparable activity with respect to cisplatin against different
human breast cancer cell lines, while upon immobilization, superior antiproliferative activity with
markedly increased cytotoxicity (more than 1000-fold lower IC50 values) compared to cisplatin was
observed. Mechanistic investigations with the most potent conjugate, cisplatin-diacetyl caffeate (1),
and the corresponding MSNs (SBA-15|1) in a 4T1 mouse breast cancer cell line showed that these
compounds induce apoptotic cell death causing strong caspase activation. In vivo, in BALB/c mice,
1 and SBA-15|1 inhibited the tumor growth while decreasing the necrotic area and lowering the
mitotic rate.
PB  - Basel: MDPI
T2  - Nanomaterials
T1  - Mesoporous Silica Nanoparticles Enhance the Anticancer Efficacy of Platinum(IV)-Phenolate Conjugates in Breast Cancer Cell Lines
IS  - 21
VL  - 12
DO  - 10.3390/nano12213767
SP  - 3767
ER  - 

@article{
author = "Predarska, Ivana and Saoud, Mohamad and Drača, Dijana and Morgan, Ibrahim and Komazec, Teodora and Eichhorn, Thomas and Mihajlović, Ekatarina and Dunđerović, Duško and Mijatović, Sanja and Maksimović-Ivanić, Danijela and Hey-Hawkins, Evamarie and Kaluđerović, Goran N.",
year = "2022",
abstract = "The main reasons for the limited clinical efficacy of the platinum(II)-based agent cisplatin
include drug resistance and significant side effects. Due to their better stability, as well as the
possibility to introduce biologically active ligands in their axial positions constructing multifunctional
prodrugs, creating platinum(IV) complexes is a tempting strategy for addressing these limitations.
Another strategy for developing chemotherapeutics with lower toxicity relies on the ability of
nanoparticles to accumulate in greater quantities in tumor tissues through passive targeting. To
combine the two approaches, three platinum(IV) conjugates based on a cisplatin scaffold containing
in the axial positions derivatives of caffeic and ferulic acid were prepared and loaded into SBA-
15 to produce the corresponding mesoporous silica nanoparticles (MSNs). The free platinum(IV)
conjugates demonstrated higher or comparable activity with respect to cisplatin against different
human breast cancer cell lines, while upon immobilization, superior antiproliferative activity with
markedly increased cytotoxicity (more than 1000-fold lower IC50 values) compared to cisplatin was
observed. Mechanistic investigations with the most potent conjugate, cisplatin-diacetyl caffeate (1),
and the corresponding MSNs (SBA-15|1) in a 4T1 mouse breast cancer cell line showed that these
compounds induce apoptotic cell death causing strong caspase activation. In vivo, in BALB/c mice,
1 and SBA-15|1 inhibited the tumor growth while decreasing the necrotic area and lowering the
mitotic rate.",
publisher = "Basel: MDPI",
journal = "Nanomaterials",
title = "Mesoporous Silica Nanoparticles Enhance the Anticancer Efficacy of Platinum(IV)-Phenolate Conjugates in Breast Cancer Cell Lines",
number = "21",
volume = "12",
doi = "10.3390/nano12213767",
pages = "3767"
}

Predarska, I., Saoud, M., Drača, D., Morgan, I., Komazec, T., Eichhorn, T., Mihajlović, E., Dunđerović, D., Mijatović, S., Maksimović-Ivanić, D., Hey-Hawkins, E.,& Kaluđerović, G. N.. (2022). Mesoporous Silica Nanoparticles Enhance the Anticancer Efficacy of Platinum(IV)-Phenolate Conjugates in Breast Cancer Cell Lines. in Nanomaterials
Basel: MDPI., 12(21), 3767.
https://doi.org/10.3390/nano12213767

Predarska I, Saoud M, Drača D, Morgan I, Komazec T, Eichhorn T, Mihajlović E, Dunđerović D, Mijatović S, Maksimović-Ivanić D, Hey-Hawkins E, Kaluđerović GN. Mesoporous Silica Nanoparticles Enhance the Anticancer Efficacy of Platinum(IV)-Phenolate Conjugates in Breast Cancer Cell Lines. in Nanomaterials. 2022;12(21):3767.
doi:10.3390/nano12213767 .

Predarska, Ivana, Saoud, Mohamad, Drača, Dijana, Morgan, Ibrahim, Komazec, Teodora, Eichhorn, Thomas, Mihajlović, Ekatarina, Dunđerović, Duško, Mijatović, Sanja, Maksimović-Ivanić, Danijela, Hey-Hawkins, Evamarie, Kaluđerović, Goran N., "Mesoporous Silica Nanoparticles Enhance the Anticancer Efficacy of Platinum(IV)-Phenolate Conjugates in Breast Cancer Cell Lines" in Nanomaterials, 12, no. 21 (2022):3767,
https://doi.org/10.3390/nano12213767 . .

TY  - JOUR
AU  - Paskaš, Svetlana
AU  - Murganić, Blagoje
AU  - Kuhnert, Robert
AU  - Hey-Hawkins, Evamarie
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
PY  - 2022
UR  - https://www.mdpi.com/1420-3049/27/14/4503
UR  - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC9321230
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5088
AB  - Lipoxygenases convert polyunsaturated fatty acids into biologically active metabolites such as inflammatory mediators-prostaglandins and leukotrienes. The inhibition of lipoxygenases is increasingly employed in the treatment of cancer. We evaluated the anticancer potential of two novel 5-lipoxygenase inhibitors, named CarbZDNaph and CarbZDChin, which are analogues of the commercially available inhibitor Rev-5901. The in vitro segment of this study was conducted on a mouse colorectal carcinoma cell line-CT26CL25. For an in vivo model, we induced tumors in BALB/c mice by the implantation of CT26CL25 cells, and we treated the animals with potential inhibitors. A 48 h treatment resulted in diminished cell viability. Calculated IC50 values (half-maximal inhibitory concentrations) were 25 μM, 15 μM and 30 μM for CarbZDNaph, CarbZDChin and Rev-5901, respectively. The detailed analysis of mechanism revealed an induction of caspase-dependent apoptosis and autophagy. In the presence of chloroquine, an autophagy inhibitor, we observed an increased mortality of cells, implying a cytoprotective role of autophagy. Our in vivo experiment reports tumor growth attenuation in animals treated with CarbZDChin. Compounds CarbZDNaph and Rev-5901 lacked an in vivo efficacy. The results presented in this study display a strong effect of compound CarbZDChin on malignant cell growth. Having in mind the important role of inflammation in cancer development, these results have a significant impact and are worthy of further evaluation.
PB  - Basel: MDPI
T2  - Molecules (Basel, Switzerland)
T1  - Carborane-Based Analog of Rev-5901 Attenuates Growth of Colon Carcinoma In Vivo.
IS  - 14
VL  - 27
DO  - 10.3390/molecules27144503
SP  - 4503
ER  - 

@article{
author = "Paskaš, Svetlana and Murganić, Blagoje and Kuhnert, Robert and Hey-Hawkins, Evamarie and Mijatović, Sanja and Maksimović-Ivanić, Danijela",
year = "2022",
abstract = "Lipoxygenases convert polyunsaturated fatty acids into biologically active metabolites such as inflammatory mediators-prostaglandins and leukotrienes. The inhibition of lipoxygenases is increasingly employed in the treatment of cancer. We evaluated the anticancer potential of two novel 5-lipoxygenase inhibitors, named CarbZDNaph and CarbZDChin, which are analogues of the commercially available inhibitor Rev-5901. The in vitro segment of this study was conducted on a mouse colorectal carcinoma cell line-CT26CL25. For an in vivo model, we induced tumors in BALB/c mice by the implantation of CT26CL25 cells, and we treated the animals with potential inhibitors. A 48 h treatment resulted in diminished cell viability. Calculated IC50 values (half-maximal inhibitory concentrations) were 25 μM, 15 μM and 30 μM for CarbZDNaph, CarbZDChin and Rev-5901, respectively. The detailed analysis of mechanism revealed an induction of caspase-dependent apoptosis and autophagy. In the presence of chloroquine, an autophagy inhibitor, we observed an increased mortality of cells, implying a cytoprotective role of autophagy. Our in vivo experiment reports tumor growth attenuation in animals treated with CarbZDChin. Compounds CarbZDNaph and Rev-5901 lacked an in vivo efficacy. The results presented in this study display a strong effect of compound CarbZDChin on malignant cell growth. Having in mind the important role of inflammation in cancer development, these results have a significant impact and are worthy of further evaluation.",
publisher = "Basel: MDPI",
journal = "Molecules (Basel, Switzerland)",
title = "Carborane-Based Analog of Rev-5901 Attenuates Growth of Colon Carcinoma In Vivo.",
number = "14",
volume = "27",
doi = "10.3390/molecules27144503",
pages = "4503"
}

Paskaš, S., Murganić, B., Kuhnert, R., Hey-Hawkins, E., Mijatović, S.,& Maksimović-Ivanić, D.. (2022). Carborane-Based Analog of Rev-5901 Attenuates Growth of Colon Carcinoma In Vivo.. in Molecules (Basel, Switzerland)
Basel: MDPI., 27(14), 4503.
https://doi.org/10.3390/molecules27144503

Paskaš S, Murganić B, Kuhnert R, Hey-Hawkins E, Mijatović S, Maksimović-Ivanić D. Carborane-Based Analog of Rev-5901 Attenuates Growth of Colon Carcinoma In Vivo.. in Molecules (Basel, Switzerland). 2022;27(14):4503.
doi:10.3390/molecules27144503 .

Paskaš, Svetlana, Murganić, Blagoje, Kuhnert, Robert, Hey-Hawkins, Evamarie, Mijatović, Sanja, Maksimović-Ivanić, Danijela, "Carborane-Based Analog of Rev-5901 Attenuates Growth of Colon Carcinoma In Vivo." in Molecules (Basel, Switzerland), 27, no. 14 (2022):4503,
https://doi.org/10.3390/molecules27144503 . .

TY  - JOUR
AU  - Useini, Liridona
AU  - Mojić, Marija
AU  - Laube, Markus
AU  - Lönnecke, Peter
AU  - Dahme, Jonas
AU  - Sárosi, Menyhárt B.
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Pietzsch, Jens
AU  - Hey-Hawkins, Evamarie
PY  - 2022
UR  - https://pubs.acs.org/doi/10.1021/acsomega.2c01523
UR  - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC9301635
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5075
AB  - Mefenamic acid represents a widely used nonsteroidal anti-inflammatory drug (NSAID) to treat the pain of postoperative surgery and heavy menstrual bleeding. Like other NSAIDs, mefenamic acid inhibits the synthesis of prostaglandins by nonselectively blocking cyclooxygenase (COX) isoforms COX-1 and COX-2. For the improved selectivity of the drug and, therefore, reduced related side effects, the carborane analogues of mefenamic acid were evaluated. The ortho-, meta-, and para-carborane derivatives were synthesized in three steps: halogenation of the respective cluster, followed by a Pd-catalyzed B-N coupling and hydrolysis of the nitrile derivatives under acidic conditions. The COX inhibitory activity and cytotoxicity for different cancer cell lines revealed that the carborane analogues have stronger antitumor potential compared to their parent organic compound.
PB  - Washington: American Chemical Society
T2  - ACS Omega
T1  - Carboranyl Analogues of Mefenamic Acid and Their Biological Evaluation.
IS  - 28
VL  - 7
DO  - 10.1021/acsomega.2c01523
SP  - 24282
EP  - 24291
ER  - 

@article{
author = "Useini, Liridona and Mojić, Marija and Laube, Markus and Lönnecke, Peter and Dahme, Jonas and Sárosi, Menyhárt B. and Mijatović, Sanja and Maksimović-Ivanić, Danijela and Pietzsch, Jens and Hey-Hawkins, Evamarie",
year = "2022",
abstract = "Mefenamic acid represents a widely used nonsteroidal anti-inflammatory drug (NSAID) to treat the pain of postoperative surgery and heavy menstrual bleeding. Like other NSAIDs, mefenamic acid inhibits the synthesis of prostaglandins by nonselectively blocking cyclooxygenase (COX) isoforms COX-1 and COX-2. For the improved selectivity of the drug and, therefore, reduced related side effects, the carborane analogues of mefenamic acid were evaluated. The ortho-, meta-, and para-carborane derivatives were synthesized in three steps: halogenation of the respective cluster, followed by a Pd-catalyzed B-N coupling and hydrolysis of the nitrile derivatives under acidic conditions. The COX inhibitory activity and cytotoxicity for different cancer cell lines revealed that the carborane analogues have stronger antitumor potential compared to their parent organic compound.",
publisher = "Washington: American Chemical Society",
journal = "ACS Omega",
title = "Carboranyl Analogues of Mefenamic Acid and Their Biological Evaluation.",
number = "28",
volume = "7",
doi = "10.1021/acsomega.2c01523",
pages = "24282-24291"
}

Useini, L., Mojić, M., Laube, M., Lönnecke, P., Dahme, J., Sárosi, M. B., Mijatović, S., Maksimović-Ivanić, D., Pietzsch, J.,& Hey-Hawkins, E.. (2022). Carboranyl Analogues of Mefenamic Acid and Their Biological Evaluation.. in ACS Omega
Washington: American Chemical Society., 7(28), 24282-24291.
https://doi.org/10.1021/acsomega.2c01523

Useini L, Mojić M, Laube M, Lönnecke P, Dahme J, Sárosi MB, Mijatović S, Maksimović-Ivanić D, Pietzsch J, Hey-Hawkins E. Carboranyl Analogues of Mefenamic Acid and Their Biological Evaluation.. in ACS Omega. 2022;7(28):24282-24291.
doi:10.1021/acsomega.2c01523 .

Useini, Liridona, Mojić, Marija, Laube, Markus, Lönnecke, Peter, Dahme, Jonas, Sárosi, Menyhárt B., Mijatović, Sanja, Maksimović-Ivanić, Danijela, Pietzsch, Jens, Hey-Hawkins, Evamarie, "Carboranyl Analogues of Mefenamic Acid and Their Biological Evaluation." in ACS Omega, 7, no. 28 (2022):24282-24291,
https://doi.org/10.1021/acsomega.2c01523 . .

TY  - JOUR
AU  - Kuhnert, Robert
AU  - Kuhnert, Lydia
AU  - Sárosi, Menyhárt‐B.
AU  - George, Sven
AU  - Drača, Dijana
AU  - Paskaš, Svetlana
AU  - Hofmann, Bettina
AU  - Steinhilber, Dieter
AU  - Honscha, Walther
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Hey-Hawkins, Evamarie
PY  - 2022
UR  - https://onlinelibrary.wiley.com/doi/10.1002/cmdc.202100588
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4686
AB  - 12-Lipoxygenase is crucial for tumour angiogenesis. 5,6,7-Trihydroxy-2-phenyl-4H-1-benzopyran-4-one (baicalein) is a suitable inhibitor for this enzyme but is rapidly metabolised in vivo. Thus, an improvement of the metabolic stability is necessary to enhance the therapeutic efficiency. An emerging approach to enhance metabolic stability of carbon-based pharmaceuticals is the use of metabolically stable, non-toxic boron clusters, such as dicarba-closo-dodecaborane(12)s (carboranes) as phenyl mimetics. Therefore, the unsubstituted phenyl ring of baicalein was replaced by meta-carborane, resulting in borcalein, the carborane analogue of baicalein. This substitution resulted in a decreased inhibitory activity toward 12-lipoxygenase, but led to increased toxicity in melanoma (A375, B16, B16F10) and colon cancer cell lines (SW480, HCT116, CT26CL25) with decreased tumour selectivity in comparison to baicalein. Surprisingly, borcalein displays a different mechanism of cytotoxicity with increased intracellular production of reactive oxygen species (ROS), reactive nitrogen species (RNS) and nitric oxide (NO).
PB  - Weinheim: John Wiley and Sons Ltd.
T2  - ChemMedChem
T1  - Borcalein: a Carborane-Based Analogue of Baicalein with 12-Lipoxygenase-Independent Toxicity
IS  - 1
VL  - 17
DO  - 10.1002/cmdc.202100588
SP  - e202100588
ER  - 

@article{
author = "Kuhnert, Robert and Kuhnert, Lydia and Sárosi, Menyhárt‐B. and George, Sven and Drača, Dijana and Paskaš, Svetlana and Hofmann, Bettina and Steinhilber, Dieter and Honscha, Walther and Mijatović, Sanja and Maksimović-Ivanić, Danijela and Hey-Hawkins, Evamarie",
year = "2022",
abstract = "12-Lipoxygenase is crucial for tumour angiogenesis. 5,6,7-Trihydroxy-2-phenyl-4H-1-benzopyran-4-one (baicalein) is a suitable inhibitor for this enzyme but is rapidly metabolised in vivo. Thus, an improvement of the metabolic stability is necessary to enhance the therapeutic efficiency. An emerging approach to enhance metabolic stability of carbon-based pharmaceuticals is the use of metabolically stable, non-toxic boron clusters, such as dicarba-closo-dodecaborane(12)s (carboranes) as phenyl mimetics. Therefore, the unsubstituted phenyl ring of baicalein was replaced by meta-carborane, resulting in borcalein, the carborane analogue of baicalein. This substitution resulted in a decreased inhibitory activity toward 12-lipoxygenase, but led to increased toxicity in melanoma (A375, B16, B16F10) and colon cancer cell lines (SW480, HCT116, CT26CL25) with decreased tumour selectivity in comparison to baicalein. Surprisingly, borcalein displays a different mechanism of cytotoxicity with increased intracellular production of reactive oxygen species (ROS), reactive nitrogen species (RNS) and nitric oxide (NO).",
publisher = "Weinheim: John Wiley and Sons Ltd.",
journal = "ChemMedChem",
title = "Borcalein: a Carborane-Based Analogue of Baicalein with 12-Lipoxygenase-Independent Toxicity",
number = "1",
volume = "17",
doi = "10.1002/cmdc.202100588",
pages = "e202100588"
}

Kuhnert, R., Kuhnert, L., Sárosi, Menyhárt‐B., George, S., Drača, D., Paskaš, S., Hofmann, B., Steinhilber, D., Honscha, W., Mijatović, S., Maksimović-Ivanić, D.,& Hey-Hawkins, E.. (2022). Borcalein: a Carborane-Based Analogue of Baicalein with 12-Lipoxygenase-Independent Toxicity. in ChemMedChem
Weinheim: John Wiley and Sons Ltd.., 17(1), e202100588.
https://doi.org/10.1002/cmdc.202100588

Kuhnert R, Kuhnert L, Sárosi M, George S, Drača D, Paskaš S, Hofmann B, Steinhilber D, Honscha W, Mijatović S, Maksimović-Ivanić D, Hey-Hawkins E. Borcalein: a Carborane-Based Analogue of Baicalein with 12-Lipoxygenase-Independent Toxicity. in ChemMedChem. 2022;17(1):e202100588.
doi:10.1002/cmdc.202100588 .

Kuhnert, Robert, Kuhnert, Lydia, Sárosi, Menyhárt‐B., George, Sven, Drača, Dijana, Paskaš, Svetlana, Hofmann, Bettina, Steinhilber, Dieter, Honscha, Walther, Mijatović, Sanja, Maksimović-Ivanić, Danijela, Hey-Hawkins, Evamarie, "Borcalein: a Carborane-Based Analogue of Baicalein with 12-Lipoxygenase-Independent Toxicity" in ChemMedChem, 17, no. 1 (2022):e202100588,
https://doi.org/10.1002/cmdc.202100588 . .

TY  - CONF
AU  - Drača, Dijana
AU  - Predarska, Ivana
AU  - Komazec, Teodora
AU  - Mihajlović, Ekatarina
AU  - Kaluđerović, Goran N.
AU  - Mijatović, Sanja
AU  - Hey-Hawkins, Evamarie
AU  - Maksimović-Ivanić, Danijela
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5288
AB  - Severe side effects and drug resistance are the main obstacles in clinical usage of cisplatin. The preparation of platinum(IV) prodrugs and the use of nanoparticles might be potential paths for overcoming the problem of toxicity. Caffeic acid is plant metabolite with many pharmacological effects such as antiinflammatory, anticancer, and hepatoprotective1. In this study, a hybrid molecule build up from cisplatin and acetylated caffeic acid, free and loaded into nanoparticles, SBA-15, was evaluated as an anticancer agent. Cytotoxic studies revealed that free conjugate possessed similar activity as cisplatin alone against 4T1 cell line, while upon imobilisation in SBA-15, much improved cytotoxicity was noticed. Further investigation showed that these compounds induced caspase-dependent apoptosis and an accumulation of cells in the subG compartment of the cell cycle. Intensive production of oxygen and nitrogen radicals was also observed. Also, survived clones lost their dividing potential. Mode of action of this cisplatin-caffeic acid conjugate against 4T1 cells makes it valuable in futher research, from the side of enhancement of its antitumour activity upon mobilisation into nanoparticles and potential reduced toxicity in vivo.
PB  - Belgrade: Faculty of Chemistry
C3  - Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia
T1  - Mesoporous silica nanoparticles improve the antitumour activity of cisplatin-acetylated caffeic acid conjugate
SP  - 62
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5288
ER  - 

@conference{
author = "Drača, Dijana and Predarska, Ivana and Komazec, Teodora and Mihajlović, Ekatarina and Kaluđerović, Goran N. and Mijatović, Sanja and Hey-Hawkins, Evamarie and Maksimović-Ivanić, Danijela",
year = "2022",
abstract = "Severe side effects and drug resistance are the main obstacles in clinical usage of cisplatin. The preparation of platinum(IV) prodrugs and the use of nanoparticles might be potential paths for overcoming the problem of toxicity. Caffeic acid is plant metabolite with many pharmacological effects such as antiinflammatory, anticancer, and hepatoprotective1. In this study, a hybrid molecule build up from cisplatin and acetylated caffeic acid, free and loaded into nanoparticles, SBA-15, was evaluated as an anticancer agent. Cytotoxic studies revealed that free conjugate possessed similar activity as cisplatin alone against 4T1 cell line, while upon imobilisation in SBA-15, much improved cytotoxicity was noticed. Further investigation showed that these compounds induced caspase-dependent apoptosis and an accumulation of cells in the subG compartment of the cell cycle. Intensive production of oxygen and nitrogen radicals was also observed. Also, survived clones lost their dividing potential. Mode of action of this cisplatin-caffeic acid conjugate against 4T1 cells makes it valuable in futher research, from the side of enhancement of its antitumour activity upon mobilisation into nanoparticles and potential reduced toxicity in vivo.",
publisher = "Belgrade: Faculty of Chemistry",
journal = "Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia",
title = "Mesoporous silica nanoparticles improve the antitumour activity of cisplatin-acetylated caffeic acid conjugate",
pages = "62",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5288"
}

Drača, D., Predarska, I., Komazec, T., Mihajlović, E., Kaluđerović, G. N., Mijatović, S., Hey-Hawkins, E.,& Maksimović-Ivanić, D.. (2022). Mesoporous silica nanoparticles improve the antitumour activity of cisplatin-acetylated caffeic acid conjugate. in Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia
Belgrade: Faculty of Chemistry., 62.
https://hdl.handle.net/21.15107/rcub_ibiss_5288

Drača D, Predarska I, Komazec T, Mihajlović E, Kaluđerović GN, Mijatović S, Hey-Hawkins E, Maksimović-Ivanić D. Mesoporous silica nanoparticles improve the antitumour activity of cisplatin-acetylated caffeic acid conjugate. in Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia. 2022;:62.
https://hdl.handle.net/21.15107/rcub_ibiss_5288 .

Drača, Dijana, Predarska, Ivana, Komazec, Teodora, Mihajlović, Ekatarina, Kaluđerović, Goran N., Mijatović, Sanja, Hey-Hawkins, Evamarie, Maksimović-Ivanić, Danijela, "Mesoporous silica nanoparticles improve the antitumour activity of cisplatin-acetylated caffeic acid conjugate" in Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia (2022):62,
https://hdl.handle.net/21.15107/rcub_ibiss_5288 .

TY  - CONF
AU  - Mihajlović, Ekatarina
AU  - Drača, Dijana
AU  - Komazec, Teodora
AU  - Mijatović, Sanja
AU  - Predarska, Ivana
AU  - Kaluđerović, Goran N.
AU  - Hey-Hawkins, Evamarie
AU  - Maksimović-Ivanić, Danijela
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5287
AB  - To develop anticancer drugs with higher activity and reduced toxicity, cisplatin was used as a scaffold to bear the anti-inflammatory drug naproxen and this conjugate was loaded into silica nanoparticles, SBA-15. In this study, the cytotoxic effect of the free conjugate and the one loaded in SBA-15 was evaluated on different cancer cell lines of mouse origin (B16, 4T1, CT26 and MC38). Treatment with free, as well as with SBA-15-bound conjugate, dose-dependently decreased viability of all cancer cell lines. The viability decrease of B16 cells after treatment with both agents was not caused by apoptosis, but it was followed by caspase activation. On the other hand, treatment with both agents caused significant decrease of B16 cells division rate, indicating the primary cytostatic effect of these agents. Additionally, it was shown that treatment with the free conjugate caused intensified autophagy, while the conjugate loaded into SBA-15 did not show this effect. Since the viability of cells recovered upon the exposure to 3-methyl adenine, detected autophagy serves as a cell death mechanism. Overall, these results indicate that both nacked and immobilized conjugates show great potential for cancer treatment.
PB  - Belgrade: Faculty of Chemistry
C3  - Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia
T1  - Anticancer properties of cisplatin-naproxen conjugate: free and loaded in SBA-15
SP  - 99
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5287
ER  - 

@conference{
author = "Mihajlović, Ekatarina and Drača, Dijana and Komazec, Teodora and Mijatović, Sanja and Predarska, Ivana and Kaluđerović, Goran N. and Hey-Hawkins, Evamarie and Maksimović-Ivanić, Danijela",
year = "2022",
abstract = "To develop anticancer drugs with higher activity and reduced toxicity, cisplatin was used as a scaffold to bear the anti-inflammatory drug naproxen and this conjugate was loaded into silica nanoparticles, SBA-15. In this study, the cytotoxic effect of the free conjugate and the one loaded in SBA-15 was evaluated on different cancer cell lines of mouse origin (B16, 4T1, CT26 and MC38). Treatment with free, as well as with SBA-15-bound conjugate, dose-dependently decreased viability of all cancer cell lines. The viability decrease of B16 cells after treatment with both agents was not caused by apoptosis, but it was followed by caspase activation. On the other hand, treatment with both agents caused significant decrease of B16 cells division rate, indicating the primary cytostatic effect of these agents. Additionally, it was shown that treatment with the free conjugate caused intensified autophagy, while the conjugate loaded into SBA-15 did not show this effect. Since the viability of cells recovered upon the exposure to 3-methyl adenine, detected autophagy serves as a cell death mechanism. Overall, these results indicate that both nacked and immobilized conjugates show great potential for cancer treatment.",
publisher = "Belgrade: Faculty of Chemistry",
journal = "Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia",
title = "Anticancer properties of cisplatin-naproxen conjugate: free and loaded in SBA-15",
pages = "99",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5287"
}

Mihajlović, E., Drača, D., Komazec, T., Mijatović, S., Predarska, I., Kaluđerović, G. N., Hey-Hawkins, E.,& Maksimović-Ivanić, D.. (2022). Anticancer properties of cisplatin-naproxen conjugate: free and loaded in SBA-15. in Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia
Belgrade: Faculty of Chemistry., 99.
https://hdl.handle.net/21.15107/rcub_ibiss_5287

Mihajlović E, Drača D, Komazec T, Mijatović S, Predarska I, Kaluđerović GN, Hey-Hawkins E, Maksimović-Ivanić D. Anticancer properties of cisplatin-naproxen conjugate: free and loaded in SBA-15. in Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia. 2022;:99.
https://hdl.handle.net/21.15107/rcub_ibiss_5287 .

Mihajlović, Ekatarina, Drača, Dijana, Komazec, Teodora, Mijatović, Sanja, Predarska, Ivana, Kaluđerović, Goran N., Hey-Hawkins, Evamarie, Maksimović-Ivanić, Danijela, "Anticancer properties of cisplatin-naproxen conjugate: free and loaded in SBA-15" in Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia (2022):99,
https://hdl.handle.net/21.15107/rcub_ibiss_5287 .

TY  - CONF
AU  - Komazec, Teodora
AU  - Drača, Dijana
AU  - Mijatović, Sanja
AU  - Predarska, Ivana
AU  - Kaluđerović, Goran N.
AU  - Hey-Hawkins, Evamarie
AU  - Maksimović-Ivanić, Danijela
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5284
AB  - From its discovery, cisplatin therapy has widely been associated with toxicity and severe side effects. Platinum(IV) complexes, as well as immobilising them in nanomaterials could help to overcome these problems. Cyclooxygenase-2 (COX-2) is involved in cancer progresssion,1 which encourages the development of inhibitors of COX enzymes in antitumour therapy. To determine the potential cytotoxic effect, a cisplatin-ibuprofen conjugate in free form, as well as loaded into SBA-15 nanomaterial, was tested on 4T1, CT26, B16 and MC38 cell lines. The results of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and crystal violet viability assays showed that both agents dose-dependently decreased the number of viable cells of all tested cell lines. Flow cytometric analysis revealed significant decrease in the division potential of B16-treated cells. In further investigations, activation of caspases proved by ApoStat assay was noticed; however, apoptosis was not identified by flow cytometry in culture of treated B16 cells. Finally, light microscopy evaluation revealed the presence of enlarged cells with prominent heterochromatin foci in nuclei upon the treatment indicating that cells entered senescent state. High antitumour potential defined at the nanomolar concentration on mouse melanoma cells make cisplatin-ibuprofen a suitable candidate for further research.
PB  - Belgrade: Faculty of Chemistry
C3  - Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia
T1  - Cisplatin-ibuprofen conjugate free and immobilised in mesoporous silica nanoparticle SBA-15 indicate high antiproliferative potential on mouse cancer cell lines
SP  - 83
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5284
ER  - 

@conference{
author = "Komazec, Teodora and Drača, Dijana and Mijatović, Sanja and Predarska, Ivana and Kaluđerović, Goran N. and Hey-Hawkins, Evamarie and Maksimović-Ivanić, Danijela",
year = "2022",
abstract = "From its discovery, cisplatin therapy has widely been associated with toxicity and severe side effects. Platinum(IV) complexes, as well as immobilising them in nanomaterials could help to overcome these problems. Cyclooxygenase-2 (COX-2) is involved in cancer progresssion,1 which encourages the development of inhibitors of COX enzymes in antitumour therapy. To determine the potential cytotoxic effect, a cisplatin-ibuprofen conjugate in free form, as well as loaded into SBA-15 nanomaterial, was tested on 4T1, CT26, B16 and MC38 cell lines. The results of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and crystal violet viability assays showed that both agents dose-dependently decreased the number of viable cells of all tested cell lines. Flow cytometric analysis revealed significant decrease in the division potential of B16-treated cells. In further investigations, activation of caspases proved by ApoStat assay was noticed; however, apoptosis was not identified by flow cytometry in culture of treated B16 cells. Finally, light microscopy evaluation revealed the presence of enlarged cells with prominent heterochromatin foci in nuclei upon the treatment indicating that cells entered senescent state. High antitumour potential defined at the nanomolar concentration on mouse melanoma cells make cisplatin-ibuprofen a suitable candidate for further research.",
publisher = "Belgrade: Faculty of Chemistry",
journal = "Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia",
title = "Cisplatin-ibuprofen conjugate free and immobilised in mesoporous silica nanoparticle SBA-15 indicate high antiproliferative potential on mouse cancer cell lines",
pages = "83",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5284"
}

Komazec, T., Drača, D., Mijatović, S., Predarska, I., Kaluđerović, G. N., Hey-Hawkins, E.,& Maksimović-Ivanić, D.. (2022). Cisplatin-ibuprofen conjugate free and immobilised in mesoporous silica nanoparticle SBA-15 indicate high antiproliferative potential on mouse cancer cell lines. in Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia
Belgrade: Faculty of Chemistry., 83.
https://hdl.handle.net/21.15107/rcub_ibiss_5284

Komazec T, Drača D, Mijatović S, Predarska I, Kaluđerović GN, Hey-Hawkins E, Maksimović-Ivanić D. Cisplatin-ibuprofen conjugate free and immobilised in mesoporous silica nanoparticle SBA-15 indicate high antiproliferative potential on mouse cancer cell lines. in Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia. 2022;:83.
https://hdl.handle.net/21.15107/rcub_ibiss_5284 .

Komazec, Teodora, Drača, Dijana, Mijatović, Sanja, Predarska, Ivana, Kaluđerović, Goran N., Hey-Hawkins, Evamarie, Maksimović-Ivanić, Danijela, "Cisplatin-ibuprofen conjugate free and immobilised in mesoporous silica nanoparticle SBA-15 indicate high antiproliferative potential on mouse cancer cell lines" in Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia (2022):83,
https://hdl.handle.net/21.15107/rcub_ibiss_5284 .