Carbonic anhydrase inhibitors. Inhibition of the Rv1284 and Rv3273 β-carbonic anhydrases from Mycobacterium tuberculosis with diazenylbenzenesulfonamides

A series of diazenylbenzenesulfonamides obtained from sulfanilamide or metanilamide by diazotization followed by coupling with phenols or amines, was tested for the inhibition of the β-carbonic anhydrases (CAs, EC 4.2.1.1) encoded by the genes Rv1284 and Rv3273 of Mycobacterium tuberculosis. Several low micromolar inhibitors of the two enzymes were detected, with prontosil being the best inhibitor (KIs of 126–148 nM). Inhibition of pathogenic β-CAs may lead to the development of antiinfectives with a new mechanism of action, devoid of resistance problems encountered with classical antibiotics.

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