Tetrahydroquinazole-based secondary sulphonamides as carbonic anhydrase inhibitors: synthesis,biological evaluation against isoforms I,II, IV,and IX,and computational studies |
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| Authors: | Emma Baglini Rahul Ravichandran Emanuela Berrino Silvia Salerno Elisabetta Barresi Anna Maria Marini Monica Viviano Sabrina Castellano Federico Da Settimo Claudiu T Supuran Sandro Cosconati Sabrina Taliani |
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| Institution: | aDepartment of Pharmacy, University of Pisa, Pisa, Italy;bDiSTABiF, University of Campania Luigi Vanvitelli, Caserta, Italy;cNEUROFARBA Department, Sezione di Scienze Farmaceutiche e Nutraceutiche, Università degli Studi di Firenze, Sesto Fiorentino, Italy;dDepartment of Pharmacy, Epigenetic Med Chem Lab, University of Salerno, Fisciano, Italy |
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| Abstract: | A library of variously decorated N-phenyl secondary sulphonamides featuring the bicyclic tetrahydroquinazole scaffold was synthesised and biologically evaluated for their inhibitory activity against human carbonic anhydrase (hCA) I, II, IV, and IX. Of note, several compounds were identified showing submicromolar potency and excellent selectivity for the tumour-related hCA IX isoform. Structure–activity relationship data attained for various substitutions were rationalised by molecular modelling studies in terms of both inhibitory activity and selectivity. |
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| Keywords: | Carbonic anhydrases inhibitors secondary sulphonamides tetrahydroquinazole derivatives structure– activity relationships tumour-related CA IX isoform |
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