Synthesis and biological evaluation of sulfonamide‐based compounds as inhibitors of carbonic anhydrase from Vibrio cholerae

Abstract

This study reports our continued efforts to identify inhibitors capable of targeting carbonic anhydrases (CAs) expressed in bacteria. Based on previously identified chemotypes, we designed and synthesized new analogs that were screened toward the α, β, and γ classes encoded in Vibrio cholerae (Vch). The K i values measured in the stopped-flow hydrase assay revealed that very simple structural modifications might induce a relevant impact on the inhibitory effects as well as the selectivity profile over ubiquitous human isozymes (hCA I/II). Unfortunately, the best active VchCA inhibitors demonstrated a dramatic loss of hCA II selectivity when compared to previously reported compounds. Among the new series of sulfonamides, several molecules proved to be about sevenfold more potent against VchCAγ than the reference compound acetazolamide, thus furnishing new insights for further development of inhibitors targeting CAs expressed in bacteria.

Evaluation of the In Vitro Antifungal Activity of Novel Arylsulfonamides against Candida spp.

“…The four sulfonamides, 3-6, were obtained by following a previously reported procedure [17,18]; their physicochemical properties and spectroscopic data were in good agreement with previous data [17,18]. N-benzylbenzamide (10) and N-benzylbiphenyl-4-carboxamide (11) have already been reported in the literature by other authors [19,20].…”

“…The first subset of four sulfonamide-based compounds, N-(4-sulfamoylbenzyl)biphenyl-4-carboxamide (3), 2,2-diphenyl-N-(4-sulfamoylbenzyl)acetamide (4), N-(4-sulfamoylphenethyl)biphenyl-4-carboxamide (5) and 2,2-diphenyl-N-(4-sulfamoylphenethyl) acetamide (6), was retrieved in our library; therefore, these compounds were re-synthesized [17,18] by employing the synthetic procedure reported in Scheme 1, with slight modifications. In detail, these compounds were prepared with the coupling reaction of the 4-(aminomethyl) benzenesulfonamide hydrochloride (1) or 4-(aminoethyl) benzenesulfonamide ( 2) and the suitable aroyl chlorides in basic conditions.…”