{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:47:54Z","timestamp":1785415674667,"version":"3.56.0"},"reference-count":47,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008770","name":"Anadolu University","doi-asserted-by":"publisher","award":["THD-2026-3503"],"award-info":[{"award-number":["THD-2026-3503"]}],"id":[{"id":"10.13039\/501100008770","id-type":"DOI","asserted-by":"publisher"}]},{"award":["THD-2026-3503"],"award-info":[{"award-number":["THD-2026-3503"]}],"id":[{"id":"https:\/\/ror.org\/05nz37n09","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>In this study, due to the side effect profiles and low efficacy of currently used inhibitors, novel benzimidazole-oxadiazole derivatives (6a\u20136e, 7a\u20137e) were synthesized as dual inhibitors of \u03b1-GLY and AR. Their structures were elucidated using 13C-NMR and 1H-NMR techniques. Their binding properties were investigated by molecular docking studies, and their ADME properties were screened in silico. AR and \u03b1-GLY inhibitory effects of the synthesized compounds were examined. The compounds were observed to exhibit partially similar inhibitory effects to the reference drug epalrestate (IC50: 0.78 nM; KI: 0.74 \u00b1 0.0 nM) on AR inhibition. Among them, compounds 6a, 6b, and 6c showed the highest activity with KI values of 8.6 \u00b1 0.4, 3.5 \u00b1 0.3 and 6.3 \u00b1 0.5 nM, respectively. Compounds 6a and 7e were found to have higher inhibitory activity against the \u03b1-GLY enzyme than the reference drug Acarbose (IC50: 128.4 \u00b5M; KI: 96.2 \u00b1 5.7 \u00b5M) with KI values of 5.8 \u00b1 0.4 and 7.9 \u00b1 0.8 \u00b5M, respectively. Overall, the newly synthesized compounds demonstrated pronounced AR inhibitory activity and notable \u03b1-GLY inhibition. Nevertheless, further pharmacological and toxicity evaluations are required to confirm their therapeutic potential. Among the tested molecules, compounds 6a and 7e may therefore be considered potential candidates for further investigation as anti-diabetic agents.<\/jats:p>","DOI":"10.3390\/molecules31152635","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T08:16:52Z","timestamp":1785313012000},"page":"2635","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Design, Synthesis, In Silico ADME, Toxicity Prediction and Molecular Docking Studies of Benzimidazole-Oxadiazole Derivatives for \u03b1-Glucosidase and Aldose Reductase Pathways as Potent Anti-Diabetic Agents"],"prefix":"10.3390","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4677-8104","authenticated-orcid":false,"given":"Mesut","family":"I\u015f\u0131k","sequence":"first","affiliation":[{"name":"Department of Bioengineering, Faculty of Engineering, Bilecik \u015eeyh Edebali University, 11230 Bilecik, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-9619-6705","authenticated-orcid":false,"given":"Abd\u00fcllatif","family":"Karakaya","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Zonguldak Bulent Ecevit University, 67600 Zonguldak, Turkey"},{"name":"Department of Pharmaceutical Chemistry, Graduate School, Anadolu University, 26470 Eskisehir, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1879-1034","authenticated-orcid":false,"given":"Ulviye Acar","family":"\u00c7evik","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskisehir, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2092-7829","authenticated-orcid":false,"given":"Adem","family":"Necip","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Services, Vocational School of Health Services, Harran University, 63300 \u015eanl\u0131urfa, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2080-0091","authenticated-orcid":false,"given":"Hatice Esra","family":"Duran","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Faculty of Medicine, Kafkas University, 36100 Kars, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4153-1209","authenticated-orcid":false,"given":"Bilge","family":"\u00c7ift\u00e7i","sequence":"additional","affiliation":[{"name":"Vocational School of Health Services, Bilecik \u015eeyh Edebali University, 11230 Bilecik, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5948-1855","authenticated-orcid":false,"given":"Yusuf","family":"\u00d6zkay","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskisehir, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2252-0923","authenticated-orcid":false,"given":"Zafer As\u0131m","family":"Kaplanc\u0131kl\u0131","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskisehir, Turkey"},{"name":"The Rectorate of Bilecik \u015eeyh Edebali University, 11230 Bilecik, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3667-6902","authenticated-orcid":false,"given":"\u015e\u00fckr\u00fc","family":"Beydemir","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Pharmacy, Anadolu Universty, 26470 Eskisehir, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1356893","DOI":"10.1155\/2020\/1356893","article-title":"Antioxidant effects and mechanisms of medicinal plants and their bioactive compounds for the prevention and treatment of type 2 diabetes: An updated review","volume":"2020","author":"Unuofin","year":"2020","journal-title":"Oxid. 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