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The purity of the synthesized molecules was confirmed by the HPLC purity analysis and was found in the range of 93%\u2013100%. The inhibition constant (K<jats:sub>i<\/jats:sub>) against hCA I ranged from 0.75\u2009nM to 1972 nM. The sulfonamides inhibited isoform hCA II significantly, with a K<jats:sub>i<\/jats:sub> ranging from 0.09 to 56\u2009nM. Similarly, the inhibitory effects on hCA IX and XII were found with K<jats:sub>i<\/jats:sub> spanning from 27.8 to 2099\u2009nM and 9.43 to 509\u2009nM, respectively. Most of the synthesized compounds showed significant inhibition in comparison to standard drugs such as acetazolamide, ethoxzolamide, zonisamide, methazolamide, dorzolamide, and SLC\u20100111. Antioxidant activity was assessed using the DPPH assay, with compound <jats:bold>13<\/jats:bold> showing better antioxidant activity with an IC<jats:sub>50<\/jats:sub> of 54.8\u2009\u00b5g\/mL, as compared to the standard ascorbic acid (IC<jats:sub>50<\/jats:sub> 64.7\u2009\u00b5g\/mL). The molecular docking studies provided insights into the binding modes of these compounds. The in silico physicochemical properties, pharmacokinetic\/ADME, and toxicity properties evaluations confirmed favorable drug\u2010likeness properties, complying with Lipinski's rule. These findings underscore the therapeutic potential of these compounds for the treatment of retinal\/cerebral edema, glaucoma, edema, epilepsy management, high\u2010altitude sickness, and cancer.<\/jats:p>","DOI":"10.1002\/jbt.70135","type":"journal-article","created":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T10:53:17Z","timestamp":1736938397000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Design, Synthesis, and In Vitro Evaluation of Aromatic Sulfonamides as Human Carbonic Anhydrase I, II, IX, and XII Inhibitors and Their Antioxidant Activity"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5628-8224","authenticated-orcid":false,"given":"KM","family":"Abha Mishra","sequence":"first","affiliation":[{"name":"Department of Medicinal Chemistry National Institute of Pharmaceutical Education and Research Guwahati India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7571-6145","authenticated-orcid":false,"given":"Nutan","family":"Kumari","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry National Institute of Pharmaceutical Education and Research Guwahati India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1141-6146","authenticated-orcid":false,"given":"Fabrizio","family":"Carta","sequence":"additional","affiliation":[{"name":"NEUROFARBA Department, Sezione di Farmaceutica e Nutraceutica Universit\u00e0 degli Studi di Firenze Sesto Fiorentino Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9109-030X","authenticated-orcid":false,"given":"Gioele","family":"Renzi","sequence":"additional","affiliation":[{"name":"NEUROFARBA Department, Sezione di Farmaceutica e Nutraceutica Universit\u00e0 degli Studi di Firenze Sesto Fiorentino Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4262-0323","authenticated-orcid":false,"given":"Claudiu T.","family":"Supuran","sequence":"additional","affiliation":[{"name":"NEUROFARBA Department, Sezione di Farmaceutica e Nutraceutica Universit\u00e0 degli Studi di Firenze Sesto Fiorentino Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7627-0053","authenticated-orcid":false,"given":"Kalyan K.","family":"Sethi","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry National Institute of Pharmaceutical Education and Research Guwahati India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,1,15]]},"reference":[{"key":"e_1_2_10_2_1","first-page":"151","volume-title":"Chapter 8\u2014Human Carbonic Anhydrases Tissue Distribution, Physiological Role, and Druggability","author":"Nocentini A.","year":"2019"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2007.04.020"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2015.02.046"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1603112113"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41396-019-0426-8"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/14756366.2020.1755852"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.2174\/156802607780636690"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/catal10091008"},{"key":"e_1_2_10_10_1","first-page":"IX, 430","volume-title":"Subcellular Biochemistry","author":"Frost S. 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