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  - 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  - 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  - 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  - JOUR
AU  - Kuhnert, Robert
AU  - Sárosi, Menyhárt-Botond
AU  - George, Sven
AU  - Lönnecke, Peter
AU  - Hofmann, Bettina
AU  - Steinhilber, Dieter
AU  - Steinmann, Sara
AU  - Schneider-Stock, Regine
AU  - Murganić, Blagoje
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Hey-Hawkins, Evamarie
PY  - 2018
UR  - http://doi.wiley.com/10.1002/cmdc.201800651
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3225
AB  - 5-Lipoxygenase converts arachidonic acid into leukotrienes, which are involved in inflammation and angiogenesis. The introduction of carboranes can improve the pharmacokinetic behavior of metabolically less stable pharmaceutics. Herein we report the syntheses of several carborane-based inhibitors of the 5-lipoxygenase pathway. The isosteric replacement of phenyl rings by carboranes leads to improved cytotoxicity toward several melanoma and colon cancer cell lines. For the colon cancer cell line HCT116, the co-inhibition of heat shock protein 90 was observed.
T2  - ChemMedChem
T2  - ChemMedChem
T1  - Carborane-Based Analogues of 5-Lipoxygenase Inhibitors Co-inhibit Heat Shock Protein 90 in HCT116 Cells.
DO  - 10.1002/cmdc.201800651
ER  - 

@article{
author = "Kuhnert, Robert and Sárosi, Menyhárt-Botond and George, Sven and Lönnecke, Peter and Hofmann, Bettina and Steinhilber, Dieter and Steinmann, Sara and Schneider-Stock, Regine and Murganić, Blagoje and Mijatović, Sanja and Maksimović-Ivanić, Danijela and Hey-Hawkins, Evamarie",
year = "2018",
abstract = "5-Lipoxygenase converts arachidonic acid into leukotrienes, which are involved in inflammation and angiogenesis. The introduction of carboranes can improve the pharmacokinetic behavior of metabolically less stable pharmaceutics. Herein we report the syntheses of several carborane-based inhibitors of the 5-lipoxygenase pathway. The isosteric replacement of phenyl rings by carboranes leads to improved cytotoxicity toward several melanoma and colon cancer cell lines. For the colon cancer cell line HCT116, the co-inhibition of heat shock protein 90 was observed.",
journal = "ChemMedChem, ChemMedChem",
title = "Carborane-Based Analogues of 5-Lipoxygenase Inhibitors Co-inhibit Heat Shock Protein 90 in HCT116 Cells.",
doi = "10.1002/cmdc.201800651"
}

Kuhnert, R., Sárosi, M., George, S., Lönnecke, P., Hofmann, B., Steinhilber, D., Steinmann, S., Schneider-Stock, R., Murganić, B., Mijatović, S., Maksimović-Ivanić, D.,& Hey-Hawkins, E.. (2018). Carborane-Based Analogues of 5-Lipoxygenase Inhibitors Co-inhibit Heat Shock Protein 90 in HCT116 Cells.. in ChemMedChem.
https://doi.org/10.1002/cmdc.201800651

Kuhnert R, Sárosi M, George S, Lönnecke P, Hofmann B, Steinhilber D, Steinmann S, Schneider-Stock R, Murganić B, Mijatović S, Maksimović-Ivanić D, Hey-Hawkins E. Carborane-Based Analogues of 5-Lipoxygenase Inhibitors Co-inhibit Heat Shock Protein 90 in HCT116 Cells.. in ChemMedChem. 2018;.
doi:10.1002/cmdc.201800651 .

Kuhnert, Robert, Sárosi, Menyhárt-Botond, George, Sven, Lönnecke, Peter, Hofmann, Bettina, Steinhilber, Dieter, Steinmann, Sara, Schneider-Stock, Regine, Murganić, Blagoje, Mijatović, Sanja, Maksimović-Ivanić, Danijela, Hey-Hawkins, Evamarie, "Carborane-Based Analogues of 5-Lipoxygenase Inhibitors Co-inhibit Heat Shock Protein 90 in HCT116 Cells." in ChemMedChem (2018),
https://doi.org/10.1002/cmdc.201800651 . .

TY  - JOUR
AU  - Kuhnert, Robert
AU  - Sárosi, Menyhárt-Botond
AU  - George, Sven
AU  - Lönnecke, Peter
AU  - Hofmann, Bettina
AU  - Steinhilber, Dieter
AU  - Murganić, Blagoje
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Hey-Hawkins, Evamarie
PY  - 2017
UR  - http://doi.wiley.com/10.1002/cmdc.201700309
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2789
AB  - The progression of cancer is accelerated by increased proliferation, angiogenesis, and inflammation. These processes are mediated by leukotrienes. Several cancer cell lines overexpress 5-lipoxygenase, an enzyme that converts arachidonic acid into leukotrienes. An early inhibitor of the 5-lipoxygenase pathway is Rev-5901, which, however, lacks in invivo efficacy, as it is rapidly metabolized. We investigated the introduction of carboranes as highly hydrophobic and metabolically stable pharmacophores into lipoxygenase inhibitors. Carboranes are icosahedral boron clusters that are remarkably stable and used to increase the metabolic stability of unstable pharmaceutics without changing their biological activity. By introduction of meta-carborane into Rev-5901, the first carborane-based inhibitor of the 5-lipoxygenase pathway was obtained. We report the synthesis and inhibitory and cytotoxic behavior of these compounds toward several melanoma and colon cancer cell lines and their related anticancer mechanisms.
T2  - ChemMedChem
T1  - CarbORev-5901: The First Carborane-Based Inhibitor of the 5-Lipoxygenase Pathway
IS  - 13
VL  - 12
DO  - 10.1002/cmdc.201700309
SP  - 1081
EP  - 1086
ER  - 

@article{
author = "Kuhnert, Robert and Sárosi, Menyhárt-Botond and George, Sven and Lönnecke, Peter and Hofmann, Bettina and Steinhilber, Dieter and Murganić, Blagoje and Mijatović, Sanja and Maksimović-Ivanić, Danijela and Hey-Hawkins, Evamarie",
year = "2017",
abstract = "The progression of cancer is accelerated by increased proliferation, angiogenesis, and inflammation. These processes are mediated by leukotrienes. Several cancer cell lines overexpress 5-lipoxygenase, an enzyme that converts arachidonic acid into leukotrienes. An early inhibitor of the 5-lipoxygenase pathway is Rev-5901, which, however, lacks in invivo efficacy, as it is rapidly metabolized. We investigated the introduction of carboranes as highly hydrophobic and metabolically stable pharmacophores into lipoxygenase inhibitors. Carboranes are icosahedral boron clusters that are remarkably stable and used to increase the metabolic stability of unstable pharmaceutics without changing their biological activity. By introduction of meta-carborane into Rev-5901, the first carborane-based inhibitor of the 5-lipoxygenase pathway was obtained. We report the synthesis and inhibitory and cytotoxic behavior of these compounds toward several melanoma and colon cancer cell lines and their related anticancer mechanisms.",
journal = "ChemMedChem",
title = "CarbORev-5901: The First Carborane-Based Inhibitor of the 5-Lipoxygenase Pathway",
number = "13",
volume = "12",
doi = "10.1002/cmdc.201700309",
pages = "1081-1086"
}

Kuhnert, R., Sárosi, M., George, S., Lönnecke, P., Hofmann, B., Steinhilber, D., Murganić, B., Mijatović, S., Maksimović-Ivanić, D.,& Hey-Hawkins, E.. (2017). CarbORev-5901: The First Carborane-Based Inhibitor of the 5-Lipoxygenase Pathway. in ChemMedChem, 12(13), 1081-1086.
https://doi.org/10.1002/cmdc.201700309

Kuhnert R, Sárosi M, George S, Lönnecke P, Hofmann B, Steinhilber D, Murganić B, Mijatović S, Maksimović-Ivanić D, Hey-Hawkins E. CarbORev-5901: The First Carborane-Based Inhibitor of the 5-Lipoxygenase Pathway. in ChemMedChem. 2017;12(13):1081-1086.
doi:10.1002/cmdc.201700309 .

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