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

ABSTRACT: Inhibition of the ?-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 (KI 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.

SUBMITTER: Akdemir A

PROVIDER: S-EPMC6366411 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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

Akdemir Atilla A Angeli Andrea A Göktaş Füsun F Eraslan Elma Pınar P Karalı Nilgün N Supuran Claudiu T CT

Journal of enzyme inhibition and medicinal chemistry 20191201 1

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<sub>I</sub> of 6.4 nM) as well as the highest selectivity for inhibiting CgNce103 over the cytosolic human ...[more]

PMID: 30724625

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