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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Detalles Bibliográficos
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
Descripción
Sumario: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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