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Synthesis and In Vitro Biological Evaluation of p-Carborane-Based Di-tert-butylphenol Analogs
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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10254233/ https://www.ncbi.nlm.nih.gov/pubmed/37299023 http://dx.doi.org/10.3390/molecules28114547 |
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author | Braun, Sebastian Jelača, Sanja Laube, Markus George, Sven Hofmann, Bettina Lönnecke, Peter Steinhilber, Dieter Pietzsch, Jens Mijatović, Sanja Maksimović-Ivanić, Danijela Hey-Hawkins, Evamarie |
author_facet | Braun, Sebastian Jelača, Sanja Laube, Markus George, Sven Hofmann, Bettina Lönnecke, Peter Steinhilber, Dieter Pietzsch, Jens Mijatović, Sanja Maksimović-Ivanić, Danijela Hey-Hawkins, Evamarie |
author_sort | Braun, Sebastian |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-10254233 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-102542332023-06-10 Synthesis and In Vitro Biological Evaluation of p-Carborane-Based Di-tert-butylphenol Analogs Braun, Sebastian Jelača, Sanja Laube, Markus George, Sven Hofmann, Bettina Lönnecke, Peter Steinhilber, Dieter Pietzsch, Jens Mijatović, Sanja Maksimović-Ivanić, Danijela Hey-Hawkins, Evamarie Molecules Article 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. MDPI 2023-06-04 /pmc/articles/PMC10254233/ /pubmed/37299023 http://dx.doi.org/10.3390/molecules28114547 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Braun, Sebastian Jelača, Sanja Laube, Markus 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 |
title | Synthesis and In Vitro Biological Evaluation of p-Carborane-Based Di-tert-butylphenol Analogs |
title_full | Synthesis and In Vitro Biological Evaluation of p-Carborane-Based Di-tert-butylphenol Analogs |
title_fullStr | Synthesis and In Vitro Biological Evaluation of p-Carborane-Based Di-tert-butylphenol Analogs |
title_full_unstemmed | Synthesis and In Vitro Biological Evaluation of p-Carborane-Based Di-tert-butylphenol Analogs |
title_short | Synthesis and In Vitro Biological Evaluation of p-Carborane-Based Di-tert-butylphenol Analogs |
title_sort | synthesis and in vitro biological evaluation of p-carborane-based di-tert-butylphenol analogs |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10254233/ https://www.ncbi.nlm.nih.gov/pubmed/37299023 http://dx.doi.org/10.3390/molecules28114547 |
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