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New aspects of synthetic tubulysin derivative, tubugi 1, action in murine melanoma model

Drača, Dijana; Mijatović, Sanja; Krajnović, Tamara; Bogdanović Pristov, Jelena; Đukić, Tatjana; Kaluđerović, Goran N.; Wessjohann, Ludger A.; Maksimović-Ivanić, Danijela

(Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine, 2022)

TY  - CONF
AU  - Drača, Dijana
AU  - Mijatović, Sanja
AU  - Krajnović, Tamara
AU  - Bogdanović Pristov, Jelena
AU  - Đukić, Tatjana
AU  - Kaluđerović, Goran N.
AU  - Wessjohann, Ludger A.
AU  - Maksimović-Ivanić, Danijela
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5292
AB  - Tubulisins are natural peptide compounds isolated from mycobacterial genera.
They belong to the group of antimitotic agents, since they achieve their antitumor
effect disrupting the function of mitotic spindle. The object of this study was to investigate
anticancer potential of synthetic analogue of tubulysins, tubugi 1, on mouse
melanoma model, in vitro and in vivo. Tubugi 1 decreased dose-dependently viability
of B16 cells. The experimental compound induced atypical apoptosis without the externalization
of phosphatidylserines (PS). Although apoptosis was accompanied with
strong intracellular production of reactive oxygen and nitrogen species, decrease in
malonyldyaldehyde content showed that membrane lipids were not subjected to oxidation,
what is a prerequisite for the externalization of PS. Although PS plays a key
role in the removal of apoptotic cells, this did not affect the phagocytic activity of
macrophages in vitro, implying PS-independent apoptotic cells removal. The effect of
the experimental agent was confirmed in vivo. Мacrophages isolated from peritoneal
exudate of treated animals showed cytotoxic activity, what was in line with demonstrated
expression of M1 phenotype markers, as well as production of nitric oxide.
Additonally, the phagocytic activity of these cells was preserved. Having in mind lack
of data in the literature concerning the effects of this group of agents on components
of the innate immune system, tubugi 1 remains worthy of further research in the field
of experimental oncology.
AB  - Тубулизини су природна једињења изолована из родова миксобактерија.
Спадају у групу антимитотских агенаса будући да свој антитуморски ефекат
остварују на нивоу деобног вретена. У овој студији испитиван је антитумор-
ски потенцијал синтетског аналога тубулизина, тубуги 1, in vitro и in vivo на
моделу мишјег меланома. Тубуги 1 је на дозно-зависан начин смањио вијаби-
литет B16 ћелија. Експериментално једињење је у овим ћелијама индуковало
атипичну форму апоптотске ћелијске смрти без екстернализације фосфати-
дилсерина (ПС). Иако је апоптоза била праћена снажном продукцијом ре-
активних врста кисеоника и азота, смањење садржаја малонилдиалдехида је
показало да мембрански липиди нису подлегли оксидацији, што је предуслов
за екстернализацију ПС. Иако ПС има кључну улогу у уклањању апоптотских
ћелија, ово се није одразило на фагоцитну активност макрофага in vitro, ука-
зујући на фагоцитозу независну од ПС. Учинак експерименталног агенса је
потврђен in vivo. Макрофаги изоловани из перитонеалног ексудата третира-
них животиња показали су цитотоксичну активност, што је у сагласности са
показаном експресијом маркера М1 фенотипа и продукцијом азот моноксида.
Додатно, фагоцитна способност ових ћелија је била очувана. С обзиром на
недостатак података у литератури о деловању овакве групе агенаса на компо-
ненте урођеног имунског система, тубуги 1 остаје вредан даљих испитивања
на пољу експерименталне онкологије.
PB  - Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine
C3  - Abstract Book: First Serbian molecular medicine congress; 2022 Jun 16-18; Foča, Bosnia and Herzegovina
T1  - New aspects of synthetic tubulysin derivative, tubugi 1, action in murine melanoma model
SP  - 41
SP  - 42
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5292
ER  - 
@conference{
author = "Drača, Dijana and Mijatović, Sanja and Krajnović, Tamara and Bogdanović Pristov, Jelena and Đukić, Tatjana and Kaluđerović, Goran N. and Wessjohann, Ludger A. and Maksimović-Ivanić, Danijela",
year = "2022",
abstract = "Tubulisins are natural peptide compounds isolated from mycobacterial genera.
They belong to the group of antimitotic agents, since they achieve their antitumor
effect disrupting the function of mitotic spindle. The object of this study was to investigate
anticancer potential of synthetic analogue of tubulysins, tubugi 1, on mouse
melanoma model, in vitro and in vivo. Tubugi 1 decreased dose-dependently viability
of B16 cells. The experimental compound induced atypical apoptosis without the externalization
of phosphatidylserines (PS). Although apoptosis was accompanied with
strong intracellular production of reactive oxygen and nitrogen species, decrease in
malonyldyaldehyde content showed that membrane lipids were not subjected to oxidation,
what is a prerequisite for the externalization of PS. Although PS plays a key
role in the removal of apoptotic cells, this did not affect the phagocytic activity of
macrophages in vitro, implying PS-independent apoptotic cells removal. The effect of
the experimental agent was confirmed in vivo. Мacrophages isolated from peritoneal
exudate of treated animals showed cytotoxic activity, what was in line with demonstrated
expression of M1 phenotype markers, as well as production of nitric oxide.
Additonally, the phagocytic activity of these cells was preserved. Having in mind lack
of data in the literature concerning the effects of this group of agents on components
of the innate immune system, tubugi 1 remains worthy of further research in the field
of experimental oncology., Тубулизини су природна једињења изолована из родова миксобактерија.
Спадају у групу антимитотских агенаса будући да свој антитуморски ефекат
остварују на нивоу деобног вретена. У овој студији испитиван је антитумор-
ски потенцијал синтетског аналога тубулизина, тубуги 1, in vitro и in vivo на
моделу мишјег меланома. Тубуги 1 је на дозно-зависан начин смањио вијаби-
литет B16 ћелија. Експериментално једињење је у овим ћелијама индуковало
атипичну форму апоптотске ћелијске смрти без екстернализације фосфати-
дилсерина (ПС). Иако је апоптоза била праћена снажном продукцијом ре-
активних врста кисеоника и азота, смањење садржаја малонилдиалдехида је
показало да мембрански липиди нису подлегли оксидацији, што је предуслов
за екстернализацију ПС. Иако ПС има кључну улогу у уклањању апоптотских
ћелија, ово се није одразило на фагоцитну активност макрофага in vitro, ука-
зујући на фагоцитозу независну од ПС. Учинак експерименталног агенса је
потврђен in vivo. Макрофаги изоловани из перитонеалног ексудата третира-
них животиња показали су цитотоксичну активност, што је у сагласности са
показаном експресијом маркера М1 фенотипа и продукцијом азот моноксида.
Додатно, фагоцитна способност ових ћелија је била очувана. С обзиром на
недостатак података у литератури о деловању овакве групе агенаса на компо-
ненте урођеног имунског система, тубуги 1 остаје вредан даљих испитивања
на пољу експерименталне онкологије.",
publisher = "Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine",
journal = "Abstract Book: First Serbian molecular medicine congress; 2022 Jun 16-18; Foča, Bosnia and Herzegovina",
title = "New aspects of synthetic tubulysin derivative, tubugi 1, action in murine melanoma model",
pages = "41-42",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5292"
}
Drača, D., Mijatović, S., Krajnović, T., Bogdanović Pristov, J., Đukić, T., Kaluđerović, G. N., Wessjohann, L. A.,& Maksimović-Ivanić, D.. (2022). New aspects of synthetic tubulysin derivative, tubugi 1, action in murine melanoma model. in Abstract Book: First Serbian molecular medicine congress; 2022 Jun 16-18; Foča, Bosnia and Herzegovina
Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine., 41.
https://hdl.handle.net/21.15107/rcub_ibiss_5292
Drača D, Mijatović S, Krajnović T, Bogdanović Pristov J, Đukić T, Kaluđerović GN, Wessjohann LA, Maksimović-Ivanić D. New aspects of synthetic tubulysin derivative, tubugi 1, action in murine melanoma model. in Abstract Book: First Serbian molecular medicine congress; 2022 Jun 16-18; Foča, Bosnia and Herzegovina. 2022;:41.
https://hdl.handle.net/21.15107/rcub_ibiss_5292 .
Drača, Dijana, Mijatović, Sanja, Krajnović, Tamara, Bogdanović Pristov, Jelena, Đukić, Tatjana, Kaluđerović, Goran N., Wessjohann, Ludger A., Maksimović-Ivanić, Danijela, "New aspects of synthetic tubulysin derivative, tubugi 1, action in murine melanoma model" in Abstract Book: First Serbian molecular medicine congress; 2022 Jun 16-18; Foča, Bosnia and Herzegovina (2022):41,
https://hdl.handle.net/21.15107/rcub_ibiss_5292 .

The interaction between SBA-15 derivative loaded with Ph3Sn(CH2)6OH and human melanoma A375 cell line: uptake and stem phenotype loss

Maksimović-Ivanić, Danijela; Bulatović, Mirna; Edeler, David; Bensing, Christian; Golić, Igor; Korać, Aleksandra; Kaluđerović, Goran N.; Mijatović, Sanja

(2019)

TY  - JOUR
AU  - Maksimović-Ivanić, Danijela
AU  - Bulatović, Mirna
AU  - Edeler, David
AU  - Bensing, Christian
AU  - Golić, Igor
AU  - Korać, Aleksandra
AU  - Kaluđerović, Goran N.
AU  - Mijatović, Sanja
PY  - 2019
UR  - http://link.springer.com/10.1007/s00775-019-01640-x
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3276
AB  - Extraordinary progress in medicinal inorganic chemistry in the past few years led to the rational design of novel platinum compounds, as well as nonplatinum metal-based antitumor agents, including organotin compounds, whose activity is not based on unrepairable interaction with DNA. To overcome poor solubility and toxicity problems that limited the application of these compounds numerous delivering systems were used (Lila et al. in Biol Pharm Bull 37:206–211, 2014; Yue and Cao in Curr Cancer Drug Targets 16:480–488, 2016; Duan et al. in WIREs Nanomed Nanobiotechnol 8:776–791, 2016). Regarding high drug loading capacity, mesoporous silica nanoparticles like SBA-15 became more important for targeted drug delivery. In this study, cellular uptake and biological activities responsible for organotin(IV) compound Ph3Sn(CH2)6OH (Sn6) grafted into (3-chloropropyl)triethoxysilane functionalized SBA-15 (SBA-15p → SBA-15p|Sn6) were evaluated in human melanoma A375 cell line. Moreover, the influence of SBA-15p grafted with organotin(IV) compound on the stemness of A375 cell was tested. Given the fact that SBA-15p|Sn6 nanoparticles are nonspherical and relatively large, their internalization efficiently started even after 15 min with stable adhesion to the cell membrane. After only 2 h of incubation of A375 cells with SBA-15p|Sn6 passive fluid-phase uptake and macropinocytosis were observed. Inside of the cell, treatment with SBA-15p loaded with Sn6 promoted caspase-dependent apoptosis in parallel with senescence development. The subpopulation of cells expressing Schwann-like phenotype arose upon the treatment, while the signaling pathway responsible for maintenance of pluripotency and invasiveness, Wnt, Notch1, and Oct3/4 were modulated towards less aggressive signature. In summary, SBA-15p enhances the efficacy of free Sn6 compound through efficient uptake and well profiled intracellular response followed with decreased stem characteristics of highly invasive A375 melanoma cells.
T2  - JBIC Journal of Biological Inorganic Chemistry
T1  - The interaction between SBA-15 derivative loaded with Ph3Sn(CH2)6OH and human melanoma A375 cell line: uptake and stem phenotype loss
DO  - 10.1007/s00775-019-01640-x
ER  - 
@article{
author = "Maksimović-Ivanić, Danijela and Bulatović, Mirna and Edeler, David and Bensing, Christian and Golić, Igor and Korać, Aleksandra and Kaluđerović, Goran N. and Mijatović, Sanja",
year = "2019",
abstract = "Extraordinary progress in medicinal inorganic chemistry in the past few years led to the rational design of novel platinum compounds, as well as nonplatinum metal-based antitumor agents, including organotin compounds, whose activity is not based on unrepairable interaction with DNA. To overcome poor solubility and toxicity problems that limited the application of these compounds numerous delivering systems were used (Lila et al. in Biol Pharm Bull 37:206–211, 2014; Yue and Cao in Curr Cancer Drug Targets 16:480–488, 2016; Duan et al. in WIREs Nanomed Nanobiotechnol 8:776–791, 2016). Regarding high drug loading capacity, mesoporous silica nanoparticles like SBA-15 became more important for targeted drug delivery. In this study, cellular uptake and biological activities responsible for organotin(IV) compound Ph3Sn(CH2)6OH (Sn6) grafted into (3-chloropropyl)triethoxysilane functionalized SBA-15 (SBA-15p → SBA-15p|Sn6) were evaluated in human melanoma A375 cell line. Moreover, the influence of SBA-15p grafted with organotin(IV) compound on the stemness of A375 cell was tested. Given the fact that SBA-15p|Sn6 nanoparticles are nonspherical and relatively large, their internalization efficiently started even after 15 min with stable adhesion to the cell membrane. After only 2 h of incubation of A375 cells with SBA-15p|Sn6 passive fluid-phase uptake and macropinocytosis were observed. Inside of the cell, treatment with SBA-15p loaded with Sn6 promoted caspase-dependent apoptosis in parallel with senescence development. The subpopulation of cells expressing Schwann-like phenotype arose upon the treatment, while the signaling pathway responsible for maintenance of pluripotency and invasiveness, Wnt, Notch1, and Oct3/4 were modulated towards less aggressive signature. In summary, SBA-15p enhances the efficacy of free Sn6 compound through efficient uptake and well profiled intracellular response followed with decreased stem characteristics of highly invasive A375 melanoma cells.",
journal = "JBIC Journal of Biological Inorganic Chemistry",
title = "The interaction between SBA-15 derivative loaded with Ph3Sn(CH2)6OH and human melanoma A375 cell line: uptake and stem phenotype loss",
doi = "10.1007/s00775-019-01640-x"
}
Maksimović-Ivanić, D., Bulatović, M., Edeler, D., Bensing, C., Golić, I., Korać, A., Kaluđerović, G. N.,& Mijatović, S.. (2019). The interaction between SBA-15 derivative loaded with Ph3Sn(CH2)6OH and human melanoma A375 cell line: uptake and stem phenotype loss. in JBIC Journal of Biological Inorganic Chemistry.
https://doi.org/10.1007/s00775-019-01640-x
Maksimović-Ivanić D, Bulatović M, Edeler D, Bensing C, Golić I, Korać A, Kaluđerović GN, Mijatović S. The interaction between SBA-15 derivative loaded with Ph3Sn(CH2)6OH and human melanoma A375 cell line: uptake and stem phenotype loss. in JBIC Journal of Biological Inorganic Chemistry. 2019;.
doi:10.1007/s00775-019-01640-x .
Maksimović-Ivanić, Danijela, Bulatović, Mirna, Edeler, David, Bensing, Christian, Golić, Igor, Korać, Aleksandra, Kaluđerović, Goran N., Mijatović, Sanja, "The interaction between SBA-15 derivative loaded with Ph3Sn(CH2)6OH and human melanoma A375 cell line: uptake and stem phenotype loss" in JBIC Journal of Biological Inorganic Chemistry (2019),
https://doi.org/10.1007/s00775-019-01640-x . .
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The synthetic tubulysin derivative, tubugi-1, improves the innate immune response by macrophage polarization in addition to its direct cytotoxic effects in a murine melanoma model

Drača, Dijana; Mijatović, Sanja; Krajnović, Tamara; Bogdanović Pristov, Jelena; Đukić, Tatjana; Kaluđerović, Goran N.; Wessjohann, Ludger A.; Maksimović-Ivanić, Danijela

(2019)

TY  - JOUR
AU  - Drača, Dijana
AU  - Mijatović, Sanja
AU  - Krajnović, Tamara
AU  - Bogdanović Pristov, Jelena
AU  - Đukić, Tatjana
AU  - Kaluđerović, Goran N.
AU  - Wessjohann, Ludger A.
AU  - Maksimović-Ivanić, Danijela
PY  - 2019
UR  - https://www.sciencedirect.com/science/article/pii/S0014482719302125?via%3Dihub
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3345
AB  - Synthetic tubugis are equally potent but more stable than their natural forms. Their anticancer potential was estimated on a solid melanoma in vitro and in vivo. Tubugi-1 induced the apoptosis in B16 cells accompanied with strong intracellular production of reactive species, subsequently imposing glutathione and thiol group depletion. Paradoxically, membrane lipids were excluded from the cascade of intracellular oxidation, according to malondialdehyde decrease. Although morphologically apoptosis was typical, externalization of phosphatidylserine (PS) as an early apoptotic event was not detected. Even their exposition is pivotal for apoptotic cell eradication, primary macrophages successfully eliminated PS-deficient tubugi-1 induced apoptotic cells. The tumor volume in animals exposed to the drug in therapeutic mode was reduced in comparison to control as well as to paclitaxel-treated animals. Importantly, macrophages isolated from tubugi-1 treated animals possessed conserved phagocytic activity and were functionally and phenotypically recognized as M1. The cytotoxic effect of tubugi-1 is accomplished through its ability to polarize the macrophages toward M1, probably by PS independent apoptotic cell engulfment. The unique potential of tubugi-1 to prime the innate immune response through the induction of a specific pattern of tumor cell apoptosis can be of extraordinary importance from fundamental and applicable aspects.
T2  - Experimental Cell Research
T1  - The synthetic tubulysin derivative, tubugi-1, improves the innate immune response by macrophage polarization in addition to its direct cytotoxic effects in a murine melanoma model
IS  - 2
VL  - 380
DO  - 10.1016/J.YEXCR.2019.04.028
SP  - 159
EP  - 170
ER  - 
@article{
author = "Drača, Dijana and Mijatović, Sanja and Krajnović, Tamara and Bogdanović Pristov, Jelena and Đukić, Tatjana and Kaluđerović, Goran N. and Wessjohann, Ludger A. and Maksimović-Ivanić, Danijela",
year = "2019",
abstract = "Synthetic tubugis are equally potent but more stable than their natural forms. Their anticancer potential was estimated on a solid melanoma in vitro and in vivo. Tubugi-1 induced the apoptosis in B16 cells accompanied with strong intracellular production of reactive species, subsequently imposing glutathione and thiol group depletion. Paradoxically, membrane lipids were excluded from the cascade of intracellular oxidation, according to malondialdehyde decrease. Although morphologically apoptosis was typical, externalization of phosphatidylserine (PS) as an early apoptotic event was not detected. Even their exposition is pivotal for apoptotic cell eradication, primary macrophages successfully eliminated PS-deficient tubugi-1 induced apoptotic cells. The tumor volume in animals exposed to the drug in therapeutic mode was reduced in comparison to control as well as to paclitaxel-treated animals. Importantly, macrophages isolated from tubugi-1 treated animals possessed conserved phagocytic activity and were functionally and phenotypically recognized as M1. The cytotoxic effect of tubugi-1 is accomplished through its ability to polarize the macrophages toward M1, probably by PS independent apoptotic cell engulfment. The unique potential of tubugi-1 to prime the innate immune response through the induction of a specific pattern of tumor cell apoptosis can be of extraordinary importance from fundamental and applicable aspects.",
journal = "Experimental Cell Research",
title = "The synthetic tubulysin derivative, tubugi-1, improves the innate immune response by macrophage polarization in addition to its direct cytotoxic effects in a murine melanoma model",
number = "2",
volume = "380",
doi = "10.1016/J.YEXCR.2019.04.028",
pages = "159-170"
}
Drača, D., Mijatović, S., Krajnović, T., Bogdanović Pristov, J., Đukić, T., Kaluđerović, G. N., Wessjohann, L. A.,& Maksimović-Ivanić, D.. (2019). The synthetic tubulysin derivative, tubugi-1, improves the innate immune response by macrophage polarization in addition to its direct cytotoxic effects in a murine melanoma model. in Experimental Cell Research, 380(2), 159-170.
https://doi.org/10.1016/J.YEXCR.2019.04.028
Drača D, Mijatović S, Krajnović T, Bogdanović Pristov J, Đukić T, Kaluđerović GN, Wessjohann LA, Maksimović-Ivanić D. The synthetic tubulysin derivative, tubugi-1, improves the innate immune response by macrophage polarization in addition to its direct cytotoxic effects in a murine melanoma model. in Experimental Cell Research. 2019;380(2):159-170.
doi:10.1016/J.YEXCR.2019.04.028 .
Drača, Dijana, Mijatović, Sanja, Krajnović, Tamara, Bogdanović Pristov, Jelena, Đukić, Tatjana, Kaluđerović, Goran N., Wessjohann, Ludger A., Maksimović-Ivanić, Danijela, "The synthetic tubulysin derivative, tubugi-1, improves the innate immune response by macrophage polarization in addition to its direct cytotoxic effects in a murine melanoma model" in Experimental Cell Research, 380, no. 2 (2019):159-170,
https://doi.org/10.1016/J.YEXCR.2019.04.028 . .
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(18-Crown-6)potassium(I) Trichlorido[28-acetyl-3-(tris-(hydroxylmethyl)amino-ethane)betulinic ester-κN]platinum(II): Synthesis and In Vitro Antitumor Activity

Kaluđerović, Goran; Bulatović, Mirna; Krajnović, Tamara; Paschke, Reinhard; B. Zmejkovski, Bojana; Maksimović-Ivanić, Danijela; Mijatović, Sanja

(2017)

TY  - JOUR
AU  - Kaluđerović, Goran
AU  - Bulatović, Mirna
AU  - Krajnović, Tamara
AU  - Paschke, Reinhard
AU  - B. Zmejkovski, Bojana
AU  - Maksimović-Ivanić, Danijela
AU  - Mijatović, Sanja
PY  - 2017
UR  - http://www.mdpi.com/2304-6740/5/3/56
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3042
AB  - Synthesis of platinum(II) conjugate with acetylated betulinic acid tris(hydroxymethyl)aminomethane ester (BATRIS) is presented (BATRISPt). HR-ESI-MS and multinuclear NMR spectroscopy, as well as elemental analysis were used for characterization of BATRISPt. Cytotoxicity (3-(4,5-dimethythiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), crystal violet (CV), and sulforhodamine B (SRB) assays) of BA, BATRIS, BATRISPt, and cisplatin were assessed on seven different tumor cell lines: melanoma B16, colon HCT116 and DLD-1, adenocarcinoma HeLa, breast MCF-7, and anaplastic thyroid tumor 8505C and SW1736; as well as normal MRC-5 fibroblasts. Furthermore, the effect of the mentioned compounds on the apoptosis (Annexin V/PI assay) and autophagy induction (acridine orange (AO) assay) as well as caspase 3, 8, and 9 activation were investigated on the selected B16 melanoma cell line. BATRISPt showed lower activity than BA, BATRIS, or cisplatin. All tested compounds triggered apoptosis in B16 cells. Induction of autophagy was observed in B16 cells exposed only to BATRIS. On the other hand, new conjugate activates caspases 8 and 9 in B16 cells with higher impact than BATRIS or cisplatin alone.
T2  - Inorganics
T1  - (18-Crown-6)potassium(I) Trichlorido[28-acetyl-3-(tris-(hydroxylmethyl)amino-ethane)betulinic ester-κN]platinum(II): Synthesis and In Vitro Antitumor Activity
IS  - 3
VL  - 5
DO  - 10.3390/inorganics5030056
SP  - 56
ER  - 
@article{
author = "Kaluđerović, Goran and Bulatović, Mirna and Krajnović, Tamara and Paschke, Reinhard and B. Zmejkovski, Bojana and Maksimović-Ivanić, Danijela and Mijatović, Sanja",
year = "2017",
abstract = "Synthesis of platinum(II) conjugate with acetylated betulinic acid tris(hydroxymethyl)aminomethane ester (BATRIS) is presented (BATRISPt). HR-ESI-MS and multinuclear NMR spectroscopy, as well as elemental analysis were used for characterization of BATRISPt. Cytotoxicity (3-(4,5-dimethythiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), crystal violet (CV), and sulforhodamine B (SRB) assays) of BA, BATRIS, BATRISPt, and cisplatin were assessed on seven different tumor cell lines: melanoma B16, colon HCT116 and DLD-1, adenocarcinoma HeLa, breast MCF-7, and anaplastic thyroid tumor 8505C and SW1736; as well as normal MRC-5 fibroblasts. Furthermore, the effect of the mentioned compounds on the apoptosis (Annexin V/PI assay) and autophagy induction (acridine orange (AO) assay) as well as caspase 3, 8, and 9 activation were investigated on the selected B16 melanoma cell line. BATRISPt showed lower activity than BA, BATRIS, or cisplatin. All tested compounds triggered apoptosis in B16 cells. Induction of autophagy was observed in B16 cells exposed only to BATRIS. On the other hand, new conjugate activates caspases 8 and 9 in B16 cells with higher impact than BATRIS or cisplatin alone.",
journal = "Inorganics",
title = "(18-Crown-6)potassium(I) Trichlorido[28-acetyl-3-(tris-(hydroxylmethyl)amino-ethane)betulinic ester-κN]platinum(II): Synthesis and In Vitro Antitumor Activity",
number = "3",
volume = "5",
doi = "10.3390/inorganics5030056",
pages = "56"
}
Kaluđerović, G., Bulatović, M., Krajnović, T., Paschke, R., B. Zmejkovski, B., Maksimović-Ivanić, D.,& Mijatović, S.. (2017). (18-Crown-6)potassium(I) Trichlorido[28-acetyl-3-(tris-(hydroxylmethyl)amino-ethane)betulinic ester-κN]platinum(II): Synthesis and In Vitro Antitumor Activity. in Inorganics, 5(3), 56.
https://doi.org/10.3390/inorganics5030056
Kaluđerović G, Bulatović M, Krajnović T, Paschke R, B. Zmejkovski B, Maksimović-Ivanić D, Mijatović S. (18-Crown-6)potassium(I) Trichlorido[28-acetyl-3-(tris-(hydroxylmethyl)amino-ethane)betulinic ester-κN]platinum(II): Synthesis and In Vitro Antitumor Activity. in Inorganics. 2017;5(3):56.
doi:10.3390/inorganics5030056 .
Kaluđerović, Goran, Bulatović, Mirna, Krajnović, Tamara, Paschke, Reinhard, B. Zmejkovski, Bojana, Maksimović-Ivanić, Danijela, Mijatović, Sanja, "(18-Crown-6)potassium(I) Trichlorido[28-acetyl-3-(tris-(hydroxylmethyl)amino-ethane)betulinic ester-κN]platinum(II): Synthesis and In Vitro Antitumor Activity" in Inorganics, 5, no. 3 (2017):56,
https://doi.org/10.3390/inorganics5030056 . .
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