Acyl selenoureido benzensulfonamides show potent inhibitory activity against carbonic anhydrases from the pathogenic bacterium Vibrio cholerae

Bioorg Chem. 2017 Dec:75:170-172. doi: 10.1016/j.bioorg.2017.09.016. Epub 2017 Sep 21.

Abstract

A series of acyl selenoureido benzensulfonamides was evaluated as carbonic anhydrase (CA, EC 4.2.1.1) inhibitors against two Vibrio cholerae such enzymes (VchCAα over VchCAβ) belonging to the α- and β-classes, potential novel targets for anti-infective drugs development. These compounds showed strong inhibitory action against VchCAα over VchCAβ and excellent selectivity over the human (h) off-target isoforms hCA I and II. Identification of potent and possibly selective inhibitors of VchCAα and/or VchCAβ over the human counterparts may lead to pharmacological tools useful for understanding the physiological role(s) of these under-investigated proteins, possibly involved in the virulence of the bacterium and colonization of the host in bicarbonate rich regions of the gastro-intestinal tract.

Keywords: Acylseleno-ureido; Carbonic anhydrase; Inhibitors; Metalloenzymes; Selenium; Vibrio cholerae.

MeSH terms

  • Bacterial Proteins / antagonists & inhibitors*
  • Bacterial Proteins / metabolism
  • Carbonic Anhydrase Inhibitors / chemistry*
  • Carbonic Anhydrase Inhibitors / metabolism
  • Carbonic Anhydrases / chemistry*
  • Carbonic Anhydrases / metabolism
  • Humans
  • Inhibitory Concentration 50
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / metabolism
  • Selenium / chemistry
  • Structure-Activity Relationship
  • Sulfonamides / chemistry*
  • Sulfonamides / metabolism
  • Vibrio / enzymology*

Substances

  • Bacterial Proteins
  • Carbonic Anhydrase Inhibitors
  • Isoenzymes
  • Sulfonamides
  • Carbonic Anhydrases
  • Selenium