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Structural confirmation was accomplished through <jats:sup>1<\/jats:sup>HNMR, <jats:sup>13<\/jats:sup>CNMR, and HREI\u2010MS techniques. Further, these analogues were examined for their biological activities against AChE and BuChE (Alzheimer disease). These compounds have a diverse range of potency against targeted enzymes with inhibitory concentration ranges for AChE (2.80\u2009\u00b1\u20090.30\u201321.10\u2009\u00b1\u20090.10\u2009\u03bcM) and for BuChE (3.20\u2009\u00b1\u20090.10\u201322.40\u2009\u00b1\u20090.70\u2009\u03bcM), respectively. Compounds <jats:bold>4<\/jats:bold>, <jats:bold>9<\/jats:bold>, and <jats:bold>11<\/jats:bold> emerged as the potent compounds against targeted enzymes and have inhibitory concentrations lower than donepezil (IC<jats:sub>50<\/jats:sub>\u2009=\u20095.50\u2009\u00b1\u20090.10 and 6.10\u2009\u00b1\u20090.20\u2009\u03bcM) used as a reference drug. In addition, versatile computational approaches were adopted to determine interactive properties (by molecular docking), electronic distribution and stability (through DFT calculations), and drug likeness characteristics (by ADMET predictions) of the synthesized potent scaffolds. Product confirmation was confirmed by thin layer chromatography.<\/jats:p>","DOI":"10.1111\/cbdd.70166","type":"journal-article","created":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T12:00:10Z","timestamp":1756296010000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Computationally Driven Exploration of Novel <i>bis<\/i>\u2010Thiadiazole Sulfonamides as Alzheimer's Enzyme Inhibitors: A DFT and Kinetic Perspective"],"prefix":"10.1111","volume":"106","author":[{"given":"Farman","family":"Ullah","sequence":"first","affiliation":[{"name":"Department of Chemistry Abbottabad University of Science and Technology  Abbottabad Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5404-0954","authenticated-orcid":false,"given":"Shoaib","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Chemistry Abbottabad University of Science and Technology  Abbottabad Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tayyiaba","family":"Iqbal","sequence":"additional","affiliation":[{"name":"Department of Chemistry Abbottabad University of Science and Technology  Abbottabad Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4091-271X","authenticated-orcid":false,"given":"Hamdy","family":"Kashtoh","sequence":"additional","affiliation":[{"name":"Department of Biotechnology Yeungnam University  Gyeongsan\u2010si Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eman","family":"Alzahrani","sequence":"additional","affiliation":[{"name":"Department of Chemistry, College of Science Taif University  Taif Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,8,27]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rechem.2024.101556"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cdc.2025.101193"},{"key":"e_1_2_8_4_1","first-page":"35","article-title":"The Search for Disease\u2010Modifying Treatment for Alzheimer's Disease","volume":"48","author":"Aisen P. 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