4-Sulfamoylphenylalkylamides as Inhibitors of Carbonic Anhydrases Expressed in Vibrio cholerae

0547316 - ÚOCHB 2022 RIV DE eng J - Journal Article
Mancuso, F. - De Luca, L. - Bucolo, F. - Vrábel, Milan - Angeli, A. - Capasso, C. - Supuran, C. T. - Gitto, R.
4-Sulfamoylphenylalkylamides as Inhibitors of Carbonic Anhydrases Expressed in Vibrio cholerae.
ChemMedChem. Roč. 16, č. 24 (2021), s. 3787-3794. ISSN 1860-7179. E-ISSN 1860-7187
Institutional support: RVO:61388963
Keywords : bacterial carbonic anhydrases * drug discovery * enzymes inhibitors * sulfonamides * Vibrio cholerae
OECD category: Organic chemistry
Impact factor: 3.540, year: 2021
Method of publishing: Open access
https://doi.org/10.1002/cmdc.202100510

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.
Permanent Link: http://hdl.handle.net/11104/0323578