Inhibition of the α-carbonic anhydrase from Vibrio cholerae with amides and sulfonamides incorporating imidazole moieties

Abstract

We discovered novel and selective sulfonamides/amides acting as inhibitors of the α-carbonic anhydrase (CA, EC 4.2.1.1) from the pathogenic bacterium Vibrio cholerae (VchCA). This Gram-negative bacterium is the causative agent of cholera and colonises the upper small intestine where sodium bicarbonate is present at a high concentration. The secondary sulfonamides and amides investigated here were potent, low nanomolar VchCA inhibitors whereas their inhibition of the human cytosolic isoforms CA I and II was in the micromolar range or higher. The molecules represent an interesting lead for antibacterial agents with a possibly new mechanism of action, although their CA inhibition mechanism is unknown for the moment.

Keywords:

• Carbonic anhydrase
• sulfonamide
• inhibitor
• Vibrio cholerae
• antibacterials

Disclosure statement

CTS declares conflict of interest, being author of several patents in the field of CA inhibitors/activators. This research was financed in part, by several EU projects (Euroxy, Metoxia, DeZnIt and Dynano, to CTS). The other authors do not declare conflict of interest.

Additional information

Funding

This research was financed in part, by several EU projects (Euroxy, Metoxia, DeZnIt and Dynano, to CTS).