{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T06:27:53Z","timestamp":1786429673362,"version":"build-2736575974"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Bioinform."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Diabetes mellitus is a chronic metabolic disorder characterised by persistent hyperglycemia resulting from impaired insulin secretion, action, or both. Prolonged hyperglycemia disrupts metabolic homeostasis and increases the risk of complications, including cardiovascular disease, neuropathy, nephropathy, and retinopathy. Current therapies target multiple pathways but are limited by reduced efficacy and adverse effects. Peroxisome proliferator-activated receptor gamma (PPAR\u03b3) is a key regulator of glucose and lipid metabolism and an important therapeutic target. Thiazole and isoxazole scaffolds possess antidiabetic potential, and their hybridisation may improve efficacy and safety.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To design and evaluate a novel series of thiazole-linked isoxazole derivatives targeting the alternate ligand-binding domain of PPAR\u03b3 for potential antidiabetic activity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Result<\/jats:title>\n                    <jats:p>\n                      The designed compounds (C1\u2013C210) were docked into PPAR\u03b3 (Protein Data Bank: 5 GTN), yielding nine candidates with binding affinities of \u221211.11 to \u22129.97 kcal\/mol. Reference ligands included pioglitazone, Q-35, and S-35, with C139 showing the highest affinity. Molecular dynamics simulations (200 ns) confirmed stability. Advanced Trajectory analyses indicate favourable conformational sampling, correlated residue motions, and a relatively confined conformational space.\n                      <jats:italic>In silico<\/jats:italic>\n                      drug-likeness profiling further supported their activity profile.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      In this computational study, the thiazole-linked isoxazole compound C139 demonstrated probable antidiabetic activity against PPAR\u03b3. However, these findings remain predictive and require further validation through comprehensive\n                      <jats:italic>in vitro<\/jats:italic>\n                      and\n                      <jats:italic>in vivo<\/jats:italic>\n                      studies.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fbinf.2026.1873262","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T05:35:42Z","timestamp":1786426542000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Design and in silico evaluation of Thiazole\u2013Isoxazole hybrids as PPAR\u03b3-Targeted antidiabetic agents"],"prefix":"10.3389","volume":"6","author":[{"given":"Abhirami","family":"PV","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry, NGSM Institute of Pharmaceutical Sciences (NGSMIPS), Nitte (Deemed to be University)","place":["Mangalore, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gupta Dheeraj","family":"Rajesh","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, NGSM Institute of Pharmaceutical Sciences (NGSMIPS), Nitte (Deemed to be University)","place":["Mangalore, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N. V. L. Sirisha","family":"Mulukuri","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Nitte College of Pharmaceutical Sciences (NCOPS), Nitte (Deemed to be University)","place":["Bangalore, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ranjitha","family":"A","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, NGSM Institute of Pharmaceutical Sciences (NGSMIPS), Nitte (Deemed to be University)","place":["Mangalore, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niyas","family":"Rehman","sequence":"additional","affiliation":[{"name":"Centre for Integrative Omics Data Science, Yenepoya (Deemed to be University)","place":["Mangalore, Karnataka, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiv Basant","family":"Kumar","sequence":"additional","affiliation":[{"name":"Australian Plastic Research and Innovation Lab, Global Innovative Centre for Advanced Nanomaterials (GICAN), College of Engineering, Science and Environment (CESE), The University of Newcastle","place":["Callaghan, NSW, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dileep","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education","place":["Manipal, Karnataka, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pankaj","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, NGSM Institute of Pharmaceutical Sciences (NGSMIPS), Nitte (Deemed to be University)","place":["Mangalore, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1016\/B978-0-444-53480-4.00015-1","article-title":"General aspects of diabetes mellitus","volume":"126","author":"Alam","year":"2014","journal-title":"Handb. 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