Selective inhibition of carbonic anhydrase IX by sulphonylated 1,2,3-triazole incorporated benzenesulphonamides capable of inducing apoptosis |
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| Authors: | Kiran Siwach Amit Kumar Harish Panchal Rajiv Kumar Jitender Kumar Bhardwaj Andrea Angeli Claudiu T Supuran Pawan K Sharma |
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| Institution: | aDepartment of Chemistry, Kurukshetra University, Kurukshetra, India;bReproductive Physiology Laboratory, Department of Zoology, Kurukshetra University, Kurukshetra, India;cDepartment of Chemistry, Ch. Mani Ram Godara Government College for Women, Bhodia Khera, Fatehabad, India;dDepartment of Neurosciences, Psychology, Drug Research and Child Health, Pharmaceutical and Nutraceutical Section, University of Florence, Florence, Italy |
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| 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)-1H-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. |
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| Keywords: | Carbonic anhydrase inhibitors hCA isoforms benzenesulphonamide triazole apoptosis |
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