Sulfonamide is one of the most promising classes of classical carbonic anhydrase (CA, EC 4.2.1.1) inhibitors. A novel series of indolylchalcones incorporating benzenesulfonamide-1,2,3-triazole (6a-q) has been synthesized by click chemistry reaction and investigated for hCA inhibitory activity against a panel of human carbonic anhydrases (hCAs). Most of these newly synthesized compounds exhibited interesting inhibition constants, in the nanomolar range, with some derivatives being more potent than the standard drug acetazolamide (AAZ) on hCA I isoform. Among the tested compounds, the compounds 6d (18.8 nM), 6q (38.3 nM) and 6e (50.4 nM) were 13, 6 and 5 times more potent than AAZ against hCA I isoform, respectively. Compounds 6o, 6m and 6f efficiently inhibited isoform hCA XII, with KIs in the range of 10–41.9 nM. Several compounds were also active against isoforms hCA II and hCA IX, with KIs under 100 nM. These indolylchalcone-benzenesulfonamide-1,2,3-triazole hybrids may be considered as potential leads for hCA I-selective inhibitors.

Synthesis and carbonic anhydrase inhibition studies of sulfonamide based indole-1,2,3-triazole chalcone hybrids / Singh P.; Swain B.; Thacker P.S.; Sigalapalli D.K.; Purnachander Yadav P.; Angeli A.; Supuran C.T.; Arifuddin M.. - In: BIOORGANIC CHEMISTRY. - ISSN 0045-2068. - ELETTRONICO. - 99:(2020), pp. 103839.103839-103839.103839. [10.1016/j.bioorg.2020.103839]

Synthesis and carbonic anhydrase inhibition studies of sulfonamide based indole-1,2,3-triazole chalcone hybrids

Angeli A.;Supuran C. T.;
2020

Abstract

Sulfonamide is one of the most promising classes of classical carbonic anhydrase (CA, EC 4.2.1.1) inhibitors. A novel series of indolylchalcones incorporating benzenesulfonamide-1,2,3-triazole (6a-q) has been synthesized by click chemistry reaction and investigated for hCA inhibitory activity against a panel of human carbonic anhydrases (hCAs). Most of these newly synthesized compounds exhibited interesting inhibition constants, in the nanomolar range, with some derivatives being more potent than the standard drug acetazolamide (AAZ) on hCA I isoform. Among the tested compounds, the compounds 6d (18.8 nM), 6q (38.3 nM) and 6e (50.4 nM) were 13, 6 and 5 times more potent than AAZ against hCA I isoform, respectively. Compounds 6o, 6m and 6f efficiently inhibited isoform hCA XII, with KIs in the range of 10–41.9 nM. Several compounds were also active against isoforms hCA II and hCA IX, with KIs under 100 nM. These indolylchalcone-benzenesulfonamide-1,2,3-triazole hybrids may be considered as potential leads for hCA I-selective inhibitors.
2020
99
103839
103839
Singh P.; Swain B.; Thacker P.S.; Sigalapalli D.K.; Purnachander Yadav P.; Angeli A.; Supuran C.T.; Arifuddin M.
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1305633
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