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

Journal of Enzyme Inhibition and Medicinal Chemistry

Atilla Akdemir¹  Pınar Eraslan Elma²  Füsun Göktaş²  Nilgün Karalı²  Andrea Angeli³  Claudiu T. Supuran³ 

[1] Computer-aided drug discovery laboratory, Department of Pharmacology, Faculty of Pharmacy, Bezmialem Vakif University, Istanbul, Turkey;Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Istanbul University, Istanbul, Turke;Sezione di Scienza Farmaceutiche, Neurofarba Department, Universita degli Studi di Firenze, Florence, Italy;

关键词: Sulfonamides;    Candida glabrata;    carbonic anhydrase;    docking;   

DOI  :  10.1080/14756366.2018.1564045

来源: publisher

【 摘 要 】

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 (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.

【 授权许可】

CC BY