ArticleScientific reports2017
Novel Benzylidene Thiazolidinedione Derivatives as Partial PPARγ Agonists and their Antidiabetic Effects on Type 2 Diabetes.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 53 citations in OpenAlex.
- Intracellular Pharmacokinetics of Antidiabetic Drugs: A Focused Narrative Review of Subcellular Distribution (2015-2025).Diseases (Basel, Switzerland) · 2026Review
- Pioglitazone-induced alterations of purine metabolism in healthy male subjects.Clinical and translational science · 2024Article
- Development of novel thiazolidine-2,4-dione derivatives as PPAR-γ agonists through design, synthesis, computational docking, MD simulation, and comprehensiveRSC medicinal chemistry · 2023Article
- Discovery of 5-Methylthiazole-Thiazolidinone Conjugates as Potential Anti-Inflammatory Agents: Molecular Target Identification and In Silico Studies.Molecules (Basel, Switzerland) · 2022Article
- Thiazolidin-4-Ones as Potential Antimicrobial Agents: Experimental and In Silico Evaluation.Molecules (Basel, Switzerland) · 2022Article
- Synthesis, Biological Evaluation and Molecular Docking Studies of 5-Indolylmethylen-4-oxo-2-thioxothiazolidine Derivatives.Molecules (Basel, Switzerland) · 2022Article
- The Structure Basis of Phytochemicals as Metabolic Signals for Combating Obesity.Frontiers in nutrition · 2022Review
- Therapeutic targets, novel drugs, and delivery systems for diabetes associated NAFLD and liver fibrosis.Advanced drug delivery reviews · 2021Review
- The Glitazone Class of Drugs as Carbonic Anhydrase Inhibitors-A Spin-Off Discovery from Fragment Screening.Molecules (Basel, Switzerland) · 2021Article
- Hypoglycemic and Hypolipidemic Swords: Synthesis andIranian journal of pharmaceutical research : IJPR · 2021Article
- Ectopic Overexpression of PPARγ2 in the Heart Determines Differences in Hypertrophic Cardiomyopathy After Treatment With Different Thiazolidinediones in a Mouse Model of Diabetes.Frontiers in pharmacology · 2021Article
- 5-(1Molecules (Basel, Switzerland) · 2020Article
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Authors and funding
13 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Peroxisome proliferator-activated receptor γ (PPARγ) has received significant attention as a key regulator of glucose and lipid homeostasis. In this study, we synthesized and tested a library of novel 5-benzylidene-thiazolidin-2,4-dione (BTZD) derivatives bearing a substituent on nitrogen of TZD nucleus (compounds 1a-1k, 2i-10i, 3a, 6a, and 8a-10a). Three compounds (1a, 1i, and 3a) exhibited selectivity towards PPARγ and were found to be weak to moderate partial agonists. Surface Plasmon Resonance (SPR) results demonstrated binding affinity of 1a, 1i and 3a towards PPARγ. Furthermore, docking experiments revealed that BTZDs interact with PPARγ through a distinct binding mode, forming primarily hydrophobic contacts with the ligand-binding pocket (LBD) without direct H-bonding interactions to key residues in H12 that are characteristic of full agonists. In addition, 1a, 1i and 3a significantly improved hyperglycemia and hyperlipidaemia in streptozotocin-nicotinamide (STZ-NA)-induced diabetic rats at a dose of 36 mg/kg/day administered orally for 15 days. Histopathological investigations revealed that microscopic architecture of pancreatic and hepatic cells improved in BTZDs-treated diabetic rats. These findings suggested that 1a, 1i and 3a are very promising pharmacological agents by selectively targeting PPARγ for further development in the clinical treatment of type 2 diabetes mellitus.
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