{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T16:23:19Z","timestamp":1778689399217,"version":"3.51.4"},"reference-count":41,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T00:00:00Z","timestamp":1665964800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Archiv der Pharmazie"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In recent years, multistep hybrid computational protocols have attracted attention for their application in the drug discovery of enzyme inhibitors. So far, there are large collections of human carbonic anhydrase (hCA) inhibitors, but only a few of them selectively inhibit the mitochondrial isoforms hCA VA and VB as potential therapeutics in obesity treatment. Most sulfonamide\u2010based inhibitors show poor selectivity for inhibiting isoforms of therapeutic interest over ubiquitous hCA I and hCA II. Herein, we propose a combination of ligand\u2010 and structure\u2010based approaches to generate pharmacophore models for hCA VA inhibitors. Then, we performed a virtual screening (VS) campaign on a database of commercially available sulfonamides. Finally, the in silico screening followed by docking studies suggested several \u201chit compounds\u201d that demonstrated to inhibit hCA VA at a low nanomolar concentration in a stopped\u2010flow CO<jats:sub>2<\/jats:sub> hydrase assay. Notably, the best candidate, 2\u2010(3,4\u2010dihydro\u20102<jats:italic>H<\/jats:italic>\u2010quinolin\u20101\u2010yl)\u2010<jats:italic>N<\/jats:italic>\u2010(4\u2010sulfamoylphenyl)acetamide (code name VAME\u2010<jats:bold>28<\/jats:bold>) proved to be a potent hCA VA inhibitor (<jats:italic>K<\/jats:italic><jats:sub>i<\/jats:sub> value of 54.8\u2009nM) and a more selective agent over hCA II when compared to the reference compound topiramate.<\/jats:p>","DOI":"10.1002\/ardp.202200383","type":"journal-article","created":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T08:49:27Z","timestamp":1665996567000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Structure\u2010guided identification of a selective sulfonamide\u2010based inhibitor targeting the human carbonic anhydrase VA isoform"],"prefix":"10.1002","volume":"356","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0614-5713","authenticated-orcid":false,"given":"Laura","family":"De Luca","sequence":"first","affiliation":[{"name":"Chibiofaram Department University of Messina Messina Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Angeli","sequence":"additional","affiliation":[{"name":"Neurofarba Department University of Florence Florence Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federico","family":"Ricci","sequence":"additional","affiliation":[{"name":"Chibiofaram Department University of Messina Messina Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudiu T.","family":"Supuran","sequence":"additional","affiliation":[{"name":"Neurofarba Department University of Florence Florence 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