4-Sulfamoylphenylalkylamides as Inhibitors of Carbonic Anhydrases Expressed in Vibrio cholerae
Autor: | Rosaria Gitto, Claudiu T. Supuran, Federica Bucolo, Andrea Angeli, Francesca Mancuso, Clemente Capasso, Laura De Luca, Milan Vrabel |
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Rok vydání: | 2021 |
Předmět: |
Drug
Models Molecular media_common.quotation_subject medicine.disease_cause Biochemistry Structure-Activity Relationship Bacterial carbonic anhydrases Drug Discovery medicine Humans General Pharmacology Toxicology and Pharmaceutics Treatment resistance Carbonic Anhydrase Inhibitors Vibrio cholerae Enzymes Inhibitors Sulfonamides media_common Carbonic Anhydrases Pharmacology Dose-Response Relationship Drug Molecular Structure Chemistry Drug discovery Organic Chemistry Cholera toxin Antimicrobial Molecular Medicine Acetazolamide medicine.drug |
Zdroj: | ChemMedChem (2021): 3787–3794. doi:10.1002/cmdc.202100510 info:cnr-pdr/source/autori:Mancuso F.; De Luca L.; Bucolo F.; Vrabel M.; Angeli A.; Capasso C.; Supuran C.T.; Gitto R./titolo:4-Sulfamoylphenylalkylamides as Inhibitors of Carbonic Anhydrases Expressed in Vibrio cholerae/doi:10.1002%2Fcmdc.202100510/rivista:ChemMedChem (Print)/anno:2021/pagina_da:3787/pagina_a:3794/intervallo_pagine:3787–3794/volume |
ISSN: | 1860-7187 |
DOI: | 10.1002/cmdc.202100510 |
Popis: | 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 (VchCA?, VchCA?, and VchCA?). 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 VchCA? class, for which few inhibitors are currently reported in literature. The best interesting VchCA? 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. |
Databáze: | OpenAIRE |
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