Synthesis and biological evaluation of novel 8-substituted quinoline-2-carboxamides as carbonic anhydrase inhibitors

Abstract

A series of novel 8-substituted-N-(4-sulfamoylphenyl)quinoline-2-carboxamides was synthesised by the reaction of 8-hydroxy-N-(4-sulfamoylphenyl) quinoline-2-carboxamide with alkyl and benzyl halides. The compounds were assayed for carbonic anhydrase (CA) inhibitory activity against four hCA isoforms, hCA I, hCA II, hCA IV, and hCA IX. Barring hCA IX, all the isoforms were inhibited from low to high nanomolar range. hCA I was inhibited in the range of 61.9–8126 nM, with compound 5h having an inhibition constant of KI = 61.9 nM. hCA II was inhibited in the range of 33.0–8759 nM, with compound 5h having an inhibition constant of 33.0 nM and compounds 5a and 5b having inhibition constants of 88.4 and 85.7 nM, respectively. hCA IV was inhibited in the range of 657.2–6757 nM. Hence, compound 5h, possessing low nanomolar hCA I and II inhibition, can be selected as a lead for the design of novel CA I and II inhibitors.

Keywords

• carbonic anhydrases
• metalloenzyme
• sulfonamides
• quinoline
• tail approach