A current issue of antimicrobial therapy is the resistance to treatment with worldwide consequences. Thus, the identification of innovative targets is an intriguing challenge in the drug and development process aimed at newer antimicrobial agents. The state-of-art of anticholera therapy might comprise the reduction of the expression of cholera toxin, which could be reached through the inhibition of carbonic anhydrases expressed in Vibrio cholerae (VchCAα, VchCAβ, and VchCAγ). Therefore, we focused our interest on the exploitation of sulfonamides as VchCA inhibitors. We planned to design and synthesize new benzenesulfonamides based on our knowledge of the VchCA catalytic site. The synthesized compounds were tested thus collecting useful SAR information. From our investigation, we identified new potent VchCA inhibitors, some of them displayed high affinity toward VchCAγ class, for which few inhibitors are currently reported in literature. The best interesting VchCAγ inhibitor (S)-N-(1-oxo-1-((4-sulfamoylbenzyl)amino)propan-2-yl)furan-2-carboxamide (40) resulted more active and selective inhibitor when compared with acetazolamide (AAZ) as well as previously reported VchCA inhibitors.

• Keywords
• Bacterial carbonic anhydrases, Drug Discovery, Enzymes Inhibitors, Sulfonamides, Vibrio cholerae,
• MeSH
• Benzenesulfonamides MeSH
• Carbonic Anhydrase Inhibitors chemical synthesis   chemistry   pharmacology   MeSH
• Carbonic Anhydrases genetics   metabolism   MeSH
• Humans MeSH
• Models, Molecular MeSH
• Molecular Structure MeSH
• Sulfonamides chemical synthesis   chemistry   pharmacology   MeSH
• Vibrio cholerae drug effects   genetics   MeSH
• Dose-Response Relationship, Drug MeSH
• Structure-Activity Relationship MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Carbonic Anhydrase Inhibitors MeSH
• Carbonic Anhydrases MeSH
• Sulfonamides MeSH