{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T08:06:25Z","timestamp":1789027585022,"version":"build-2803163510"},"reference-count":58,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004410","name":"T\u00fcrkiye Bilimsel ve Teknolojik Ara\u015et\u0131rma Kurumu","doi-asserted-by":"publisher","award":["324S296"],"award-info":[{"award-number":["324S296"]}],"id":[{"id":"10.13039\/501100004410","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Drug Development Research"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    In this study, 12 novel sulfonamide derivatives incorporating 2\u2010amino\u20101,3,4\u2010oxadiazole and 1,3\u2010benzazol\u20102(3\n                    <jats:italic>H<\/jats:italic>\n                    )\u2010one scaffolds were synthesized and structurally characterized using\n                    <jats:sup>1<\/jats:sup>\n                    H NMR,\n                    <jats:sup>13<\/jats:sup>\n                    C NMR, and LC\u2013MS analyses. Their inhibitory activities were evaluated against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), carbonic anhydrase I and II (CA I and CA II), and \u03b1\u2010glucosidase. Owing to their potent inhibitory profiles, enzyme kinetic studies were performed to determine inhibition constants (\n                    <jats:italic>Ki<\/jats:italic>\n                    ) and inhibition mechanisms. The synthesized compounds exhibited potent nanomolar cholinesterase inhibition. Compound\n                    <jats:bold>5b<\/jats:bold>\n                    was identified as the most active AChE inhibitor (IC\n                    <jats:sub>50<\/jats:sub>\n                    = 32.6\u2009\u00b1\u20092.6\u2009nM;\n                    <jats:italic>K\u1d62<\/jats:italic>\n                    \u2009=\u20097.1\u2009\u00b1\u20090.6\u2009nM), acting through a competitive inhibition mechanism, whereas compound\n                    <jats:bold>5g<\/jats:bold>\n                    showed the strongest BChE inhibition (IC\n                    <jats:sub>50<\/jats:sub>\n                    = 34.6\u2009\u00b1\u20092.8\u2009nM;\n                    <jats:italic>K\u1d62<\/jats:italic>\n                    \u2009=\u20098.4\u2009\u00b1\u20090.8\u2009nM) with a mixed\u2010type inhibition profile. The derivatives also displayed significant carbonic anhydrase inhibition, with compound\n                    <jats:bold>6d<\/jats:bold>\n                    emerging as the most potent inhibitor, particularly against CA II (IC\n                    <jats:sub>50<\/jats:sub>\n                    = 0.9\u2009\u00b1\u20090.06\u2009\u03bcM;\n                    <jats:italic>K\u1d62<\/jats:italic>\n                    \u2009=\u20090.43\u2009\u00b1\u20090.037\u2009\u03bcM), while exhibiting competitive inhibition and strong activity against both CA isoforms. In contrast, \u03b1\u2010glucosidase inhibition was generally weak, with compound\n                    <jats:bold>5d<\/jats:bold>\n                    showing the highest activity (IC\n                    <jats:sub>50<\/jats:sub>\n                    = 250.5\u2009\u00b1\u200921.32\u2009\u03bcM). Molecular docking studies revealed favorable binding interactions within the catalytic sites of cholinesterase and carbonic anhydrase enzymes, while 200\u2009ns length molecular dynamics simulations confirmed the stability of representative protein\u2013ligand complexes. In silico ADMET and drug\u2010likeness predictions using SwissADME and pkCSM indicated generally acceptable oral drug\u2010likeness. Compound\n                    <jats:bold>6c<\/jats:bold>\n                    exhibited the most balanced predicted pharmacokinetic profile, whereas\n                    <jats:bold>6d<\/jats:bold>\n                    , despite its excellent enzyme inhibition, showed potential limitations associated with higher polarity, limited predicted blood\u2013brain barrier penetration, and predicted toxicity risks. Overall, these findings identify the synthesized sulfonamide derivatives as promising scaffolds for the further development of multifunctional cholinesterase and carbonic anhydrase inhibitors.\n                  <\/jats:p>","DOI":"10.1002\/ddr.70375","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T08:14:50Z","timestamp":1787645690000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sulfonamide\u2010Based 2\u2010Amino\u20101,3,4\u2010Oxadiazole Derivatives as Dual Cholinesterase and Carbonic Anhydrase Inhibitors: Design, Synthesis, Kinetic Characterization, Molecular Modeling, and ADMET Evaluation"],"prefix":"10.1002","volume":"87","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9054-7437","authenticated-orcid":false,"given":"G\u00fclnur","family":"Arslan Karahan","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy Suleyman Demirel University Isparta T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8548-9703","authenticated-orcid":false,"given":"Ba\u015fak","family":"G\u00f6k\u00e7e","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Pharmacy Suleyman Demirel University Isparta T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0050-5271","authenticated-orcid":false,"given":"Muhammed Tilahun","family":"Muhammed","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy Suleyman Demirel University Isparta T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4979-349X","authenticated-orcid":false,"given":"Emre Kadir","family":"Ayan","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy Suleyman 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