Carbonic anhydrase inhibitors. Inhibition of the Rv1284 and Rv3273 beta-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 beta-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 (K(I)s of 126-148nM). Inhibition of pathogenic beta-CAs may lead to the development of antiinfectives with a new mechanism of action, devoid of resistance problems encountered with classical antibiotics.
Maresca
Alfonso
A
Università degli Studi di Firenze, Laboratorio di Chimica Bioinorganica, Via della Lastruccia 3, Sesto Fiorentino, Florence, Italy.
Carta
Fabrizio
F
Vullo
Daniela
D
Scozzafava
Andrea
A
Supuran
Claudiu T
CT
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002256:Carbonic Anhydrases / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000201:enzymology* / Q000235:genetics; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000096926:Benzenesulfonamides
D000900:Anti-Bacterial Agents; D002257:Carbonic Anhydrase Inhibitors; D002256:Carbonic Anhydrases; D011994:Recombinant Proteins; D013449:Sulfonamides; D000096926:Benzenesulfonamides