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  - 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 .

Kuhnert, Robert, Sárosi, Menyhárt-Botond, George, Sven, Lönnecke, Peter, Hofmann, Bettina, Steinhilber, Dieter, Murganić, Blagoje, Mijatović, Sanja, Maksimović-Ivanić, Danijela, Hey-Hawkins, Evamarie, "CarbORev-5901: The First Carborane-Based Inhibitor of the 5-Lipoxygenase Pathway" in ChemMedChem, 12, no. 13 (2017):1081-1086,
https://doi.org/10.1002/cmdc.201700309 . .