Selective inhibition of carbonic anhydrase IX by sulphonylated 1, 2, 3-triazole incorporated benzenesulphonamides capable of inducing apoptosis. (31st December 2022)

• Record Type: Journal Article
• Authors: Siwach, Kiran; Kumar, Amit; Panchal, Harish; Kumar, Rajiv; Bhardwaj, Jitender Kumar; Angeli, Andrea; Supuran, Claudiu T.; Sharma, Pawan K.
• Is Part Of: Journal of enzyme inhibition and medicinal chemistry. Volume 37:Number 1(2022)
• Page Start: 1454
• Page End: 1463
• Publication Date: 2022-12-31
• Subjects: Carbonic anhydrase inhibitors -- hCA isoforms -- benzenesulphonamide -- triazole -- apoptosis; Enzyme inhibitors -- Periodicals; Enzyme Inhibitors -- periodicals; Biochemistry -- periodicals; 572.7
• DOI: 10.1080/14756366.2022.2077333
• Languages: English
• ISSNs: 1475-6366

Abstract

Abstract: In search of selective carbonic anhydrase (CA) IX inhibitors endowed with apoptotic inducing properties, we designed and synthesised two subsets of 4- and 3-(5-aryl-(4-phenylsulphonyl)-1 H -1, 2, 3-triazol-1-yl)benzenesulphonamides. All compounds were assayed for human carbonic anhydrase (hCA) isoforms I, II, IV, and IX inhibition. Isoforms hCA I and hCA IV were weakly inhibited by most of the synthesised compounds. Many four-substituted benzenesulphonamides displayed low nanomolar inhibition against isoform hCA II, unlike the three-substituted analogues. All target compounds exhibited good inhibition profile with KI values ranging from 16.4 to 66.0 nM against tumour-associated isoform hCA IX. Some selective and potent inhibitors of hCA IX were assayed for in vitro apoptotic induction in goat testicular cells. Compounds 10d and 10h showed interesting apoptotic induction potential. The present study may provide insights into a strategy for the design of novel anticancer agents based on hCA inhibitors endowed with apoptotic interference.