Novel 2-indolinones containing a sulfonamide moiety as selective inhibitors of candida β-carbonic anhydrase enzyme

Inhibition of the β-carbonic anhydrase (CA, EC 4.2.1.1) from pathogenic Candida glabrata (CgNce103) by 1H-indole-2,3-dione 3-[N-(4-sulfamoylphenyl)thiosemicarbazones] 4a–m was investigated. All the compounds were found to be potent inhibitors of CgNce103, with inhibition constants in the range of 6....

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Autores principales: Akdemir, Atilla, Angeli, Andrea, Göktaş, Füsun, Eraslan Elma, Pınar, Karalı, Nilgün, Supuran, Claudiu T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2019
Materias:
Research Paper
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6366411/
https://www.ncbi.nlm.nih.gov/pubmed/30724625
http://dx.doi.org/10.1080/14756366.2018.1564045
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author Akdemir, Atilla
Angeli, Andrea
Göktaş, Füsun
Eraslan Elma, Pınar
Karalı, Nilgün
Supuran, Claudiu T.
author_facet Akdemir, Atilla
Angeli, Andrea
Göktaş, Füsun
Eraslan Elma, Pınar
Karalı, Nilgün
Supuran, Claudiu T.
author_sort Akdemir, Atilla
collection PubMed
description Inhibition of the β-carbonic anhydrase (CA, EC 4.2.1.1) from pathogenic Candida glabrata (CgNce103) by 1H-indole-2,3-dione 3-[N-(4-sulfamoylphenyl)thiosemicarbazones] 4a–m was investigated. All the compounds were found to be potent inhibitors of CgNce103, with inhibition constants in the range of 6.4-63.9 nM. The 5,7-dichloro substituted derivative 4l showed the most effective inhibition (K(I) of 6.4 nM) as well as the highest selectivity for inhibiting CgNce103 over the cytosolic human (h) isoforms hCA I and II. A possible binding interaction of compound 4l within the active site of CgNce103 has been proposed based on docking studies.
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spelling pubmed-63664112019-02-15 Novel 2-indolinones containing a sulfonamide moiety as selective inhibitors of candida β-carbonic anhydrase enzyme Akdemir, Atilla Angeli, Andrea Göktaş, Füsun Eraslan Elma, Pınar Karalı, Nilgün Supuran, Claudiu T. J Enzyme Inhib Med Chem Research Paper Inhibition of the β-carbonic anhydrase (CA, EC 4.2.1.1) from pathogenic Candida glabrata (CgNce103) by 1H-indole-2,3-dione 3-[N-(4-sulfamoylphenyl)thiosemicarbazones] 4a–m was investigated. All the compounds were found to be potent inhibitors of CgNce103, with inhibition constants in the range of 6.4-63.9 nM. The 5,7-dichloro substituted derivative 4l showed the most effective inhibition (K(I) of 6.4 nM) as well as the highest selectivity for inhibiting CgNce103 over the cytosolic human (h) isoforms hCA I and II. A possible binding interaction of compound 4l within the active site of CgNce103 has been proposed based on docking studies. Taylor & Francis 2019-02-06 /pmc/articles/PMC6366411/ /pubmed/30724625 http://dx.doi.org/10.1080/14756366.2018.1564045 Text en © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Paper
Akdemir, Atilla
Angeli, Andrea
Göktaş, Füsun
Eraslan Elma, Pınar
Karalı, Nilgün
Supuran, Claudiu T.
Novel 2-indolinones containing a sulfonamide moiety as selective inhibitors of candida β-carbonic anhydrase enzyme
title Novel 2-indolinones containing a sulfonamide moiety as selective inhibitors of candida β-carbonic anhydrase enzyme
title_full Novel 2-indolinones containing a sulfonamide moiety as selective inhibitors of candida β-carbonic anhydrase enzyme
title_fullStr Novel 2-indolinones containing a sulfonamide moiety as selective inhibitors of candida β-carbonic anhydrase enzyme
title_full_unstemmed Novel 2-indolinones containing a sulfonamide moiety as selective inhibitors of candida β-carbonic anhydrase enzyme
title_short Novel 2-indolinones containing a sulfonamide moiety as selective inhibitors of candida β-carbonic anhydrase enzyme
title_sort novel 2-indolinones containing a sulfonamide moiety as selective inhibitors of candida β-carbonic anhydrase enzyme
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6366411/
https://www.ncbi.nlm.nih.gov/pubmed/30724625
http://dx.doi.org/10.1080/14756366.2018.1564045
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