{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T06:13:01Z","timestamp":1775542381561,"version":"3.50.1"},"reference-count":46,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T00:00:00Z","timestamp":1761091200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Umm Al-Qura University, Saudi Arabia","award":["25UQU4290670GSSR06"],"award-info":[{"award-number":["25UQU4290670GSSR06"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: In this research work, novel pyrazolone-derived oxadiazole-based benzamide derivatives (1\u201310) were synthesized through unique and facile synthetic routes. Introduction: These scaffolds were designed to be therapeutically more effective and have fewer side effects. Methods: To confirm the structure of analogs in detail, we employed 1HNMR, 13CNMR, and HREI-MS spectroscopy. The potential of all derivatives was tested by screening them against alpha-amylase and alpha-glucosidase in comparison with reference anti-diabetic drug acarbose (4.50 \u00b1 0.20 \u00b5M and 4.90 \u00b1 0.30 \u00b5M). Results &amp; Discussion: Among all tested analogs and standard drugs, derivative 3 proved to be the most promising candidate. It exhibited the most powerful inhibitory effect (IC50 = 3.20 \u00b1 0.20 \u00b5M and 3.60 \u00b1 0.10 \u00b5M). To further investigate its activity, the experimental results were supported by in silico investigations. Molecular docking demonstrated strong and viable interactions between enzymes and the most potent compound. DFT calculations validated the electronic configuration, stability, and reactivity of lead molecules. Furthermore, the ADMET profile predicted the favorable drug likeness properties and low toxicity. The results of docking were further confirmed via molecular dynamics analysis, whereas the pharmacophore model of analog 3 supports the formation of a stable hydrogen bond network of derivatives with the receptor site of the enzyme. Conclusions: Collectively in silico and in vitro results underscore the therapeutic potential of these derivatives for the effective treatment of diabetes in the future.<\/jats:p>","DOI":"10.3390\/ph18111595","type":"journal-article","created":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T01:14:02Z","timestamp":1761182042000},"page":"1595","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["From Bench to Bioactivity: An Integrated Medicinal Development Based on Kinetic and Simulation Assessment of Pyrazolone-Oxadiazole Coupled Benzamide as Promising Inhibitors of Diabetes Mellitus"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5294-2193","authenticated-orcid":false,"given":"Manal M.","family":"Khowdiary","sequence":"first","affiliation":[{"name":"Department of Chemistry, Faculty of Applied Science, University College-Al Leith, University of Umm Al-Qura, Makkah 21955, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shifa","family":"Felemban","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Applied Science, University College-Al Leith, University of Umm Al-Qura, Makkah 21955, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"32234","DOI":"10.1021\/acsomega.0c03871","article-title":"Discovery of novel coumarin analogs against the \u03b1-glucosidase protein target of diabetes mellitus: Pharmacophore-based QSAR, docking, and molecular dynamics simulation studies","volume":"5","author":"Maurya","year":"2020","journal-title":"ACS Omega"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/S0140-6736(24)00825-0","article-title":"Epidemiology and management of gestational diabetes","volume":"404","author":"Sweeting","year":"2024","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1168","DOI":"10.1007\/s00125-024-06102-x","article-title":"Diabetes and infection: Review of the epidemiology, mechanisms and principles of treatment","volume":"67","author":"Holt","year":"2024","journal-title":"Diabetologia"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"McElwain, C.J., McCarthy, F.P., and McCarthy, C.M. 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