{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:11:55Z","timestamp":1792789915093,"version":"4.5.0"},"reference-count":44,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T00:00:00Z","timestamp":1789776000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Princess Nourah bint Abdulrahman University Researchers Supporting Project","award":["PNURSP2026R304"],"award-info":[{"award-number":["PNURSP2026R304"]}],"id":[{"id":"https:\/\/ror.org\/05b0cyh02","id-type":"ROR","asserted-by":"crossref"}]},{"award":["PNURSP2026R304"],"award-info":[{"award-number":["PNURSP2026R304"]}],"id":[{"id":"https:\/\/ror.org\/05b0cyh02","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Type 2 diabetes mellitus (T2DM) and hyperlipidemia are interrelated metabolic disorders that significantly increase cardiovascular risk. Thiazolidinediones are known insulin sensitizers, whereas quinoline derivatives possess diverse pharmacological activities. To explore their complementary activity, we designed a novel hybrid compound integrating a thiazolidinedione core with a quinoline moiety via a carbon spacer. Materials and Methods: The hybrid molecule was synthesized through a straightforward route and structurally confirmed by spectroscopic analyses. Zebrafish (Danio rerio) were employed as an in vivo model, with hyperglycemia induced by immersion in 100 mM glucose monohydrate for 12 days. Fish were divided into treatment groups receiving 20 or 80 mg\/kg of the compound, alongside the controls. Biochemical parameters (glucose, triglycerides, insulin) and gene expression levels (NF-\u03baB, ACOX1, ACC\u03b1) were assessed. In silico docking was conducted to predict molecular interactions. Results: Treatment with the hybrid compound significantly restored glucose, triglyceride, and insulin levels. High-dose administration suppressed NF-\u03baB expression and normalized ACOX1 levels, while both low- and high-dose treatments downregulated ACC\u03b1 compared with untreated hyperglycemic controls. Computational studies supported multitarget activity through predicted binding to PPAR-\u03b1 and ACOX1. Conclusions: Quinoline-Thiazolidine-2,4-Dione demonstrated strong antihyperglycemic and antihypertriglyceridemic activities in zebrafish models, supported by in silico validation.<\/jats:p>","DOI":"10.3390\/ph19091490","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T09:01:38Z","timestamp":1789981298000},"page":"1490","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Design, Synthesis and Antihyperglycemic\/Antilipidemic Activities of Quinoline-thiazolidine-2,4-dione Hybrid"],"prefix":"10.3390","volume":"19","author":[{"given":"ElShimaa Ahmed Mohamed","family":"Abousaada","sequence":"first","affiliation":[{"name":"Chemistry Department, Faculty of Science, Menoufia University, Shebin El-Kom 32511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Asmaa","family":"Galal-Khallaf","sequence":"additional","affiliation":[{"name":"Zoology Department, Molecular Biology and Biotechnology Laboratory, Faculty of Science, Menoufia University, Shebin El-Kom 32511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Khaled","family":"Mohammed-Geba","sequence":"additional","affiliation":[{"name":"Zoology Department, Molecular Biology and Biotechnology Laboratory, Faculty of Science, Menoufia University, Shebin El-Kom 32511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Mohamed","family":"El-Bahnsawye","sequence":"additional","affiliation":[{"name":"Chemistry Department, Faculty of Science, Menoufia University, Shebin El-Kom 32511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Mona K. Abo","family":"Hussein","sequence":"additional","affiliation":[{"name":"Clinical Microbiology and Immunology Department, National Liver Institute, Menoufia University, Shebin El-Kom 32511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1160-5040","authenticated-orcid":false,"given":"Elshaymaa I.","family":"Elmongy","sequence":"additional","affiliation":[{"name":"Pharmaceutical Chemistry Department, Faculty of Pharmacy, Capital University (Formerly Helwan University), Ain Helwan, Cairo 11795, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Rania Ali Ahmed","family":"Shaltout","sequence":"additional","affiliation":[{"name":"Zoology Department, Molecular Biology and Biotechnology Laboratory, Faculty of Science, Menoufia University, Shebin El-Kom 32511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1406-282X","authenticated-orcid":false,"given":"Reem","family":"Binsuwaidan","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah Bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9496-6086","authenticated-orcid":false,"given":"Hadeer","family":"Ali","sequence":"additional","affiliation":[{"name":"Chemistry Department, Faculty of Science, Menoufia University, Shebin El-Kom 32511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6826-8933","authenticated-orcid":false,"given":"Ahmed I.","family":"El-Tantawy","sequence":"additional","affiliation":[{"name":"Research Institute for Interdisciplinary Science, Okayama University, Tsushima-naka, Kita-ku, Okayama 700-8530, Japan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Hamed","family":"Abdel-Bary","sequence":"additional","affiliation":[{"name":"Chemistry Department, Faculty of Science, Menoufia University, Shebin El-Kom 32511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1227-7931","authenticated-orcid":false,"given":"Ibrahim El","family":"Tantawy El Sayed","sequence":"additional","affiliation":[{"name":"Chemistry Department, Faculty of Science, Menoufia University, Shebin El-Kom 32511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2087","DOI":"10.1016\/S0140-6736(23)01296-5","article-title":"Diabetes: A Defining Disease of the 21st Century","volume":"401","author":"Lancet","year":"2023","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"373","DOI":"10.15537\/1658-3175.1664","article-title":"History of Diabetes Mellitus","volume":"23","author":"Ahmed","year":"2002","journal-title":"Saudi Med. 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