{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T06:44:25Z","timestamp":1775976265445,"version":"3.50.1"},"reference-count":56,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T00:00:00Z","timestamp":1758153600000},"content-version":"vor","delay-in-days":17,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    This study presents the green synthesis, pharmacological evaluation, and\n                    <jats:italic>in silico<\/jats:italic>\n                    analysis of aromatic sulfonamide derivatives for their inhibitory effects on human carbonic anhydrase (hCA) isoforms I, II, IX, and XII and their antioxidant properties. The compounds were synthesized via a one\u2010step green synthetic method using acetic acid as the solvent, providing a straightforward and environmentally considerate approach. The synthesized compounds were confirmed to have 95% to 100% purities via HPLC purity analysis. The inhibition constants (K\n                    <jats:sub>i<\/jats:sub>\n                    ) against hCA I varied between 240\u2009nM and 2185\u2009nM, while inhibition of hCA II was observed with K\n                    <jats:sub>i<\/jats:sub>\n                    values ranging from 19 to 83\u2009nM. For hCA IX and hCA XII, the K\n                    <jats:sub>i<\/jats:sub>\n                    values were found from 25 to 882\u2009nM and 8.8 to 175\u2009nM, respectively. These sulfonamides exhibited significant inhibition compared to standard carbonic anhydrase inhibitors such as acetazolamide, ethoxzolamide, zonisamide, methazolamide, dorzolamide, and SLC\u20100111. The antioxidant activity, assessed using the DPPH assay, was moderate to low, with compound\n                    <jats:bold>6<\/jats:bold>\n                    demonstrating a noteworthy IC\n                    <jats:sub>50<\/jats:sub>\n                    of 62.8\u2009\u00b5g\/mL, comparable to the IC\n                    <jats:sub>50<\/jats:sub>\n                    of ascorbic acid (64.7\u2009\u00b5g\/mL). Quantum chemical analyses, including FMO, Mulliken population analysis, and electrostatic potential, total electron density, and molecular electrostatic potential analysis, demonstrated significant electrostatic interactions and optimal charge distribution. DFT calculations revealed stable chemical behavior with favorable values for hardness, softness, electronegativity, and electrophilicity. Molecular docking studies provided insights into the binding interactions, while MD simulations (10\u2009ns) revealed the stability of the protein\u2010ligand complexes. ADMET predictions indicated favorable physicochemical properties and compliance with Lipinski's rule. These results highlight the potential of these aromatic sulfonamide derivatives as potent inhibitors of human carbonic anhydrase isoforms, with promising antioxidant activity, suggesting their potential therapeutic applications in conditions such as retinal and cerebral edema, glaucoma, epilepsy, high\u2010altitude sickness, and cancer.\n                  <\/jats:p>","DOI":"10.1002\/jbt.70497","type":"journal-article","created":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T14:25:30Z","timestamp":1758205530000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Green Synthesis of Sulfonamide Derivatives as Human Carbonic Anhydrase Isoforms I, II, IX, XII Inhibitors and Antioxidants: Comprehensive Insights From Biological Evaluation and In\u2010Depth\n                    <i>In Silico<\/i>\n                    Analysis"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5628-8224","authenticated-orcid":false,"given":"KM Abha","family":"Mishra","sequence":"first","affiliation":[{"name":"Department of Medicinal Chemistry National Institute of Pharmaceutical Education and Research Guwahati 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 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"}]},{"given":"Harshdeep","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry National Institute of Pharmaceutical Education and Research Guwahati Guwahati India"}],"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 Guwahati India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,9,18]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2023.129411"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2467"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1517\/13543776.10.5.575"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2015.02.046"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1603112113"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41396-019-0426-8"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/14756366.2020.1755852"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.2174\/156802607780636690"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/catal10091008"},{"key":"e_1_2_9_11_1","first-page":"430","volume-title":"Subcellular Biochemistry","author":"Frost S. C.","year":"2014"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2467"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-94-007-7359-2_18"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/ardp.202400748"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26216380"},{"key":"e_1_2_9_16_1","first-page":"413","article-title":"Carbonic Anhydrase Inhibition in Ophthalmology: Carbonic Anhydrases in Cornea, Lens, Retina and Lacrimal Gland","volume":"90","author":"Wistrand P. J.","year":"2000","journal-title":"EXS"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2010.07.038"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2009.01.067"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.3109\/14756366.2015.1077823"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr200176r"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.3109\/14756366.2015.1122001"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2010.05.009"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1080\/14756366.2018.1446432"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1517\/13543776.16.12.1627"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm9900523"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsmedchemlett.7b00399"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2021.116140"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2467"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2019.112019"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.3109\/14756366.2014.940933"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1080\/17460441.2020.1743676"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2012.08.019"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.4155\/fmc.14.68"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph14070693"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbt.70135"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2018.04.002"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2023.1326633"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2015.11.034"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2012.12.037"},{"issue":"4","key":"e_1_2_9_40_1","article-title":"Carbonic Anhydrase Inhibitors: Topically Acting Antiglaucoma Sulfonamides Incorporating Phthaloyl and Phthalimido Moieties","volume":"17","author":"Scozzafava A.","year":"2001","journal-title":"Drug Design and Discovery"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm00278a034"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2015.07.070"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)62326-9"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules28237782"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.3390\/pr11082248"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.10306"},{"key":"e_1_2_9_47_1","unstructured":"BIOVIA Dassault System BIOVIA Discovery Studio Package 2024(Dassault System 2024)."},{"issue":"1","key":"e_1_2_9_48_1","first-page":"1","article-title":"Molecular Dynamic Simulations and Molecular Docking as A Potential Way for Designed new Inhibitor Drug Without Resistance","volume":"21","author":"Aghajani J.","year":"2022","journal-title":"Tanaffos"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules21060748"},{"key":"e_1_2_9_50_1","volume-title":"Gaussian 09","author":"Frisch M. J.","year":"2009"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1063\/1.1740588"},{"key":"e_1_2_9_52_1","first-page":"105","volume-title":"Molecular Electrostatic Potentials","author":"Murray J. S.","year":"1996"},{"key":"e_1_2_9_53_1","unstructured":"\u201cMolinspiration \u2013 Cheminformatics www.molinspiration.com accessedFebruary 11 2024."},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-409X(00)00129-0"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep42717"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2023.135190"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23052540"}],"container-title":["Journal of Biochemical and Molecular Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbt.70497","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jbt.70497","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbt.70497","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T05:58:02Z","timestamp":1775973482000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jbt.70497"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9]]},"references-count":56,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2025,9]]}},"alternative-id":["10.1002\/jbt.70497"],"URL":"https:\/\/doi.org\/10.1002\/jbt.70497","archive":["Portico"],"relation":{},"ISSN":["1095-6670","1099-0461"],"issn-type":[{"value":"1095-6670","type":"print"},{"value":"1099-0461","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9]]},"assertion":[{"value":"2025-05-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-01","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70497"}}