Design, synthesis and anti-hyperglycemic assessments of novel 5-benzyli-denethiazolidine-2,4-dione derivatives as PPAR-? agonist

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dc.authoridAhsan, Mohamed Jawed/0000-0002-6919-5489
dc.contributor.authorAli, Amena
dc.contributor.authorAli, Abuzer
dc.contributor.authorAsati, Vivek
dc.contributor.authorKaya, Savas
dc.contributor.authorAhsan, Mohamed Jawed
dc.date.accessioned2024-10-26T18:08:09Z
dc.date.available2024-10-26T18:08:09Z
dc.date.issued2023
dc.departmentSivas Cumhuriyet Üniversitesi
dc.description.abstractThe treatment of diabetes mellitus still relies predominantly on peroxisome proliferator-activated receptor-gamma (PPAR-gamma) therapy, known for its effectiveness. In this present study, a novel series of benzylidene-linked thia-zolidine-2,4-dione compounds was conceptualized, synthesized, and subjected to assessment for their potential antidiabetic properties. Notably, among the compounds examined, 5-((Z)-4-(((E)-Propylidene)amino)benzyli-dene)thiazolidine-2,4-dione, designated as 4c, emerged as the most promising candidate, exhibiting the highest PPAR-gamma agonistic activity with an EC50 value of 0.35 +/- 0.52 mu M. Additionally, molecular docking investigations were conducted on twelve 2,4-thiazolidinedione compounds, with a pyrazole moiety incorporated, within the ligand binding domain of PPAR-gamma. Compound 4c, in particular, demonstrated a Glide XP score of-9.104, sur-passing the score of the crystal ligand (Glide XP score =-7.482). Notably, both exhibited similar interactions with key amino acids, including HIE323, SER289, and GLN286. Furthermore, three derivatives (4a-c) with promising PPAR-gamma agonistic activity and favorable molecular docking scores underwent in vivo evaluation for their capacity to lower blood glucose levels using a streptozotocin-induced diabetic mice model. In comparison to the reference drug pioglitazone, Compound 4c displayed commendable in-vivo performance across multiple parameters, encompassing serum HDL, serum LDL, serum total cholesterol, and serum triglyceride levels. Mo-lecular dynamics simulations provided insights into the impact of ligand 4c, indicating its role in enhancing protein stability and rigidity. These findings emphasize its potential as a potent protein inhibitor, thus opening novel avenues for the intelligent design of molecules with high efficacy in the management of hyperglycemia.
dc.description.sponsorshipDeanship of Scientific Research, Taif University
dc.description.sponsorshipThe researchers would like to acknowledge Deanship of Scientific Research, Taif University for funding this work.
dc.identifier.doi10.1016/j.jics.2023.101100
dc.identifier.issn0019-4522
dc.identifier.issue11
dc.identifier.scopus2-s2.0-85175584037
dc.identifier.scopusqualityQ4
dc.identifier.urihttps://doi.org/10.1016/j.jics.2023.101100
dc.identifier.urihttps://hdl.handle.net/20.500.12418/29839
dc.identifier.volume100
dc.identifier.wosWOS:001109060200001
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.language.isoen
dc.publisherElsevier
dc.relation.ispartofJournal of the Indian Chemical Society
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subjectThiazolidine-2,4-dione
dc.subjectPPAR-gamma
dc.subjectOrganic synthesis
dc.subjectAntidiabetics
dc.titleDesign, synthesis and anti-hyperglycemic assessments of novel 5-benzyli-denethiazolidine-2,4-dione derivatives as PPAR-? agonist
dc.typeArticle

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