Synthesis, Molecular Docking, and Biological Evaluation of the New Hybrids of 4-Thiazolidinone and 4(3H)-Quinazolinone Against Streptozotocin Induced Diabetic Rats

Abstract

A series of new 3-(2-substituted)-4-(oxothiazolidin-3-yl)-2-methylquinazolin-4(3H)-ones 1a–1k is synthesized by using the hybridization approach via one pot multicomponent reaction of 3-amino-2-methylquinazolin-4(3H)-one with substituted benzaldehyde, thioglycolic acid and N, N-dicyclohexylcarbodiimide in DMF media. Structures of the synthesized compounds are elucidated from the spectral data. Antidiabetic activity of the products is tested against streptozotocin induced diabetic rats at a dose of 200 mg/kg compared with standard Pioglitazone (15 mg/kg). Compounds 1b, 1d, 1f, and 1i demonstrate significant antidiabetic activity. Compounds 1b, 1d, 1f, and 1i are evaluated in vitro are tested for serum insulin, cholesterol, triglycerides, total protein, lipoprotein, and enzymes factors. Significant lowering of glycated hemoglobin level is induced by the compounds after 21 days of treatment. Mean±S.E.M. data accumulated are subjected to one-way analysis of variance (ANOVA) followed by Dunnett’s t-test. p < 0.001 was considered statistically significant. Histopathological results accumulated for the rats treated by compounds 1b, 1d and 1f confirm the significant recovery of pancreas destruction. Free energy of binding for all synthesized compounds is calculated using AutoDock 1.5.6 with peroxisome proliferator-activated receptor γ (PPAR γ; PDB ID: 4PRG). Among the synthesized compounds, 1d demonstrates significant binding energy value of −11.46 kcal/mol. The current study is expected to provide useful insight into the design of potential agents that can act as a platform for the development of future antidiabetic drugs.