{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T03:12:40Z","timestamp":1792033960349,"version":"4.4.0"},"reference-count":69,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,1,19]],"date-time":"2023-01-19T00:00:00Z","timestamp":1674086400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deanship of Scientific Research at UmmAl-QuraUniversity","award":["22UQU4331277DSR08"],"award-info":[{"award-number":["22UQU4331277DSR08"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Recent research on dipeptidyl peptidase-IV (DPP-IV) inhibitors has made it feasible to treat type 2 diabetes mellitus (T2DM) with minimal side effects. Therefore, in the present investigation, we aimed to discover and develop some coumarin-based sulphonamides as potential DPP-IV inhibitors in light of the fact that molecular hybridization of many bioactive pharmacophores frequently results in synergistic activity. Each of the proposed derivatives was subjected to an in silico virtual screening, and those that met all of the criteria and had a higher binding affinity with the DPP-IV enzyme were then subjected to wet lab synthesis, followed by an in vitro biological evaluation. The results of the pre-ADME and pre-tox predictions indicated that compounds 6e, 6f, 6h, and 6m to 6q were inferior and violated the most drug-like criteria. It was observed that 6a, 6b, 6c, 6d, 6i, 6j, 6r, 6s, and 6t displayed less binding free energy (PDB ID: 5Y7H) than the reference inhibitor and demonstrated drug-likeness properties, hence being selected for wet lab synthesis and the structures being confirmed by spectral analysis. In the in vitro enzyme assay, the standard drug Sitagliptin had an IC50 of 0.018 \u00b5M in the experiment which is the most potent. All the tested compounds also displayed significant inhibition of the DPP-IV enzyme, but 6i and 6j demonstrated 10.98 and 10.14 \u00b5M IC50 values, respectively, i.e., the most potent among the synthesized compounds. Based on our findings, we concluded that coumarin-based sulphonamide derivatives have significant DPP-IV binding ability and exhibit optimal enzyme inhibition in an in vitro enzyme assay.<\/jats:p>","DOI":"10.3390\/molecules28031004","type":"journal-article","created":{"date-parts":[[2023,1,19]],"date-time":"2023-01-19T05:50:20Z","timestamp":1674107420000},"page":"1004","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Coumarin-Based Sulfonamide Derivatives as Potential DPP-IV Inhibitors: Pre-ADME Analysis, Toxicity Profile, Computational Analysis, and In Vitro Enzyme Assay"],"prefix":"10.3390","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6654-691X","authenticated-orcid":false,"given":"Pallavi Kishor","family":"Vawhal","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry, PEA\u2019s Modern College of Pharmacy, Sector 21, Yamunanagar, Nigdi 411044, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shailaja B.","family":"Jadhav","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, PEA\u2019s Modern College of Pharmacy, Sector 21, Yamunanagar, Nigdi 411044, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumit","family":"Kaushik","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Raja Balwant Singh Engineering Technical Campus, Bichpuri, Agra 283105, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3848-4533","authenticated-orcid":false,"given":"Kahnu Charan","family":"Panigrahi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, Gayatri Institute of Science and Technology, Gyan Vihar, Gunupur 765022, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5153-0672","authenticated-orcid":false,"given":"Chandan","family":"Nayak","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, School of Pharmaceutical Education and Research, Berhampur University, Ganjam 760007, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Humaira","family":"Urmee","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Science, North South University, Dhaka 1229, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6136-9774","authenticated-orcid":false,"given":"Sharuk L.","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, N.B.S. Institute of Pharmacy, Ausa 413520, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Falak A.","family":"Siddiqui","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, N.B.S. Institute of Pharmacy, Ausa 413520, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8167-8264","authenticated-orcid":false,"given":"Fahadul","family":"Islam","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka 1207, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0274-4479","authenticated-orcid":false,"given":"Aziz","family":"Eftekhari","sequence":"additional","affiliation":[{"name":"Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz 51665118, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7782-0574","authenticated-orcid":false,"given":"Abdullah R.","family":"Alzahrani","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Makkah 4089-6928, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3458-0440","authenticated-orcid":false,"given":"Mohd Fahami Nur","family":"Azlina","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, University Kebangsaan Malaysia, Jalan Yacob Latif, Kuala Lumpur 56000, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md. Moklesur Rahman","family":"Sarker","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, State University of Bangladesh, 77 Satmasjid Road, Dhanmondi, Dhaka 1205, Bangladesh"},{"name":"Health Med Science Research Network, 3\/1, Block F, Lalmatia, Dhaka 1207, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5757-8653","authenticated-orcid":false,"given":"Ibrahim Abdel Aziz","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Makkah 4089-6928, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"389","DOI":"10.3389\/fendo.2019.00389","article-title":"Clinical Use of DPP-4 Inhibitors","volume":"10","author":"Gallwitz","year":"2019","journal-title":"Front. 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