{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T06:39:56Z","timestamp":1787985596643,"version":"build-2784847793"},"reference-count":47,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2024,9,6]],"date-time":"2024-09-06T00:00:00Z","timestamp":1725580800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Archiv der Pharmazie"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Sulfonamides are promising classical carbonic anhydrase (CA; EC 4.2.1.1) inhibitors, being used for several medical purposes such as diuretics, anticonvulsants, topically acting antiglaucoma agents, for antiobesity\u00a0and anticancer therapies. Herein, a series of chalcone\u2010based benzenesulfonamides (<jats:bold>3a\u2012m<\/jats:bold>) was synthesized and assessed for its inhibitory activity against a panel of four human carbonic anhydrases (hCA isoforms I, II, IX, and\u00a0XII). Most compounds displayed single\u2010 to double\u2010digit nanomolar inhibition constants (<jats:italic>K<\/jats:italic><jats:sub>i<\/jats:sub>s), with some derivatives being more potent and\/or selective than the standard drug acetazolamide (AAZ). Among the synthesized compounds, <jats:bold>3g<\/jats:bold> compound demonstrated the highest inhibitory activity against the hCA II isoform (<jats:italic>K<\/jats:italic><jats:sub>i<\/jats:sub>\u2009=\u20092.5\u2009nM) with 30\u2010, 9\u2010, and 11\u2010fold selectivity for hCA II over the I, IX, and XII isoforms, respectively. Structure\u2013activity relationships for different substitution patterns were analyzed. Additionally, a molecular docking study showed that compound <jats:bold>3g<\/jats:bold> bound to hCA II by coordinating with the zinc ion through the deprotonated benzenesulfonamide moiety, in addition to a hydrogen bond formed between an oxygen of the sulfonamide moiety and Thr199. Moreover, the chalcone core participated in van der Waals interactions with some active site residues, such as Ile91, Val121, and Leu198. Consequently, this report introduces a successful approach toward identifying compound <jats:bold>3g<\/jats:bold> as a highly potent and selective chalcone\u2010based benzenesulfonamide inhibitor of hCA II worthy of further investigation.<\/jats:p>","DOI":"10.1002\/ardp.202400069","type":"journal-article","created":{"date-parts":[[2024,9,6]],"date-time":"2024-09-06T10:13:00Z","timestamp":1725617580000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Chalcone\u2010based benzenesulfonamides as potent and selective inhibitors for human carbonic anhydrase II: Design, synthesis, in vitro, and in silico studies"],"prefix":"10.1002","volume":"357","author":[{"given":"Hwa Young","family":"Lee","sequence":"first","affiliation":[{"name":"BK21 FOUR Team and Integrated Research, Institute for Drug Development, College of Pharmacy Dongguk University\u2010Seoul Goyang Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7398-6155","authenticated-orcid":false,"given":"Ahmed","family":"Elkamhawy","sequence":"additional","affiliation":[{"name":"Department of Chemistry, School of Sciences and Humanities Nazarbayev University Astana Kazakhstan"},{"name":"Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy Mansoura University Mansoura Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8173-6073","authenticated-orcid":false,"given":"Ahmed A.","family":"Al\u2010Karmalawy","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy Horus University\u2010Egypt New Damietta Egypt"},{"name":"Pharmaceutical Chemistry Department, Faculty of Pharmacy Ahram Canadian University 6th of October City Giza Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hossam","family":"Nada","sequence":"additional","affiliation":[{"name":"BK21 FOUR Team and Integrated Research, Institute for Drug Development, College of Pharmacy Dongguk University\u2010Seoul Goyang Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Giovannuzzi","sequence":"additional","affiliation":[{"name":"Department of NEUROFARBA, Section of Pharmaceutical and Nutraceutical Sciences University of Florence Firenze Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudiu T.","family":"Supuran","sequence":"additional","affiliation":[{"name":"Department of NEUROFARBA, Section of Pharmaceutical and Nutraceutical Sciences University of Florence Firenze Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyeong","family":"Lee","sequence":"additional","affiliation":[{"name":"BK21 FOUR Team and Integrated Research, Institute for Drug Development, College of Pharmacy Dongguk University\u2010Seoul Goyang Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,9,6]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0163-7258(96)00198-2"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2023.1326633"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-816476-1.00008-3"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.4155\/fmc-2017-0223"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2467"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/metabo8010019"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.2174\/138161208783877910"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/bjophthalmol-2021-319530"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1586\/14737175.2015.1066675"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-94-007-7359-2_18"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm8030349"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.113.000434"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1080\/14756366.2022.2121393"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26216380"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2014-0054OC"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.040554897"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1215\/15228517-2007-001"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2009.189"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-019-0478-4"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12154-009-0023-9"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1080\/14756366.2020.1825409"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1080\/14756366.2018.1446432"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.3109\/14756366.2015.1122001"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1080\/14756366.2018.1428572"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23052540"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsmedchemlett.1c00644"},{"key":"e_1_2_8_28_1","volume-title":"Chalcones: 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Y.Lee K.Lee ACS Omega 8(2023)21769.","DOI":"10.1021\/acsomega.3c01323"}],"container-title":["Archiv der Pharmazie"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ardp.202400069","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T13:21:40Z","timestamp":1755609700000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ardp.202400069"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,6]]},"references-count":47,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2024,11]]}},"alternative-id":["10.1002\/ardp.202400069"],"URL":"https:\/\/doi.org\/10.1002\/ardp.202400069","archive":["Portico"],"relation":{},"ISSN":["0365-6233","1521-4184"],"issn-type":[{"value":"0365-6233","type":"print"},{"value":"1521-4184","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,6]]},"assertion":[{"value":"2024-01-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-08-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2400069"}}