In Silico-Guided Identification of New Potent Inhibitors of Carbonic Anhydrases Expressed in .

Carbonic anhydrases from (VchCAs) play a significant role in bacterial pathophysiological processes. Therefore, their inhibition leads to a reduction of gene expression virulence and bacterial growth impairment. Herein, we report the first ligand-based pharmacophore model as a computational tool to study selective inhibitors of the β-class of VchCA. By a virtual screening on a collection of sulfonamides, we retrieved 9 compounds that were synthesized and evaluated for their inhibitory effects against VchCAβ as well as α- and γ-classes of VchCAs and selectivity over human ubiquitous isoforms hCA I and II. Notably, all tested compounds were active inhibitors of VchCAs. The -(4-sulfamoylbenzyl)-[1,1'-biphenyl]-4-carboxamide () stood out as the most exciting inhibitor toward the β-class ( = 95.6 nM), also showing a low affinity against the tested human isoforms. By applying docking procedures, we described the binding mode of the inhibitor within the catalytic cavity of the modeled open conformation of VchCAβ.