Potent and Selective Carboxylic Acid Inhibitors of Tumor-Associated Carbonic Anhydrases IX and XII

Selective inhibition of tumor-associated carbonic anhydrase (CA; EC 4.2.1.1) isoforms IX and XII is a crucial prerequisite to develop successful anticancer therapeutics. Herein, we confirmed the efficacy of the 3-nitrobenzoic acid substructure in the design of potent and selective carboxylic acid de...

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Autores principales: Cau, Ylenia, Vullo, Daniela, Mori, Mattia, Dreassi, Elena, Supuran, Claudiu T., Botta, Maurizio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5943959/
https://www.ncbi.nlm.nih.gov/pubmed/29271882
http://dx.doi.org/10.3390/molecules23010017
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author Cau, Ylenia
Vullo, Daniela
Mori, Mattia
Dreassi, Elena
Supuran, Claudiu T.
Botta, Maurizio
author_facet Cau, Ylenia
Vullo, Daniela
Mori, Mattia
Dreassi, Elena
Supuran, Claudiu T.
Botta, Maurizio
author_sort Cau, Ylenia
collection PubMed
description Selective inhibition of tumor-associated carbonic anhydrase (CA; EC 4.2.1.1) isoforms IX and XII is a crucial prerequisite to develop successful anticancer therapeutics. Herein, we confirmed the efficacy of the 3-nitrobenzoic acid substructure in the design of potent and selective carboxylic acid derivatives as CAs inhibitors. Compound 10 emerged as the most potent inhibitor of the tumor-associated hCA IX and XII (K(i) = 16 and 82.1 nM, respectively) with a significant selectivity with respect to the wide spread hCA II. Other 3-nitrobenzoic acid derivatives showed a peculiar CA inhibition profile with a notable potency towards hCA IX.
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spelling pubmed-59439592018-11-13 Potent and Selective Carboxylic Acid Inhibitors of Tumor-Associated Carbonic Anhydrases IX and XII Cau, Ylenia Vullo, Daniela Mori, Mattia Dreassi, Elena Supuran, Claudiu T. Botta, Maurizio Molecules Article Selective inhibition of tumor-associated carbonic anhydrase (CA; EC 4.2.1.1) isoforms IX and XII is a crucial prerequisite to develop successful anticancer therapeutics. Herein, we confirmed the efficacy of the 3-nitrobenzoic acid substructure in the design of potent and selective carboxylic acid derivatives as CAs inhibitors. Compound 10 emerged as the most potent inhibitor of the tumor-associated hCA IX and XII (K(i) = 16 and 82.1 nM, respectively) with a significant selectivity with respect to the wide spread hCA II. Other 3-nitrobenzoic acid derivatives showed a peculiar CA inhibition profile with a notable potency towards hCA IX. MDPI 2017-12-22 /pmc/articles/PMC5943959/ /pubmed/29271882 http://dx.doi.org/10.3390/molecules23010017 Text en © 2017 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Cau, Ylenia
Vullo, Daniela
Mori, Mattia
Dreassi, Elena
Supuran, Claudiu T.
Botta, Maurizio
Potent and Selective Carboxylic Acid Inhibitors of Tumor-Associated Carbonic Anhydrases IX and XII
title Potent and Selective Carboxylic Acid Inhibitors of Tumor-Associated Carbonic Anhydrases IX and XII
title_full Potent and Selective Carboxylic Acid Inhibitors of Tumor-Associated Carbonic Anhydrases IX and XII
title_fullStr Potent and Selective Carboxylic Acid Inhibitors of Tumor-Associated Carbonic Anhydrases IX and XII
title_full_unstemmed Potent and Selective Carboxylic Acid Inhibitors of Tumor-Associated Carbonic Anhydrases IX and XII
title_short Potent and Selective Carboxylic Acid Inhibitors of Tumor-Associated Carbonic Anhydrases IX and XII
title_sort potent and selective carboxylic acid inhibitors of tumor-associated carbonic anhydrases ix and xii
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5943959/
https://www.ncbi.nlm.nih.gov/pubmed/29271882
http://dx.doi.org/10.3390/molecules23010017
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