Synthesis, molecular docking and anti-diabetic evaluation of 2,4-thiazolidinedione based amide derivatives

A series of thiazolidinedione based amide derivatives were designed, synthesized and docked against the PPAR gamma receptor target. 11 compounds from the series with good glide scores were selected for in vivo antidiabetic study based on streptozotocin induced diabetic rat model. It was observed that 4 compounds (6c, 6e, 6m & 6n) showed significantly good antidiabetic activity in comparison to rosiglitazone and pioglitazone as reference drugs. Compound 6c appeared as the most potent derivative in lowering blood glucose level and showed excellent interaction with SER 342, ILE 281, pi-pi interaction with ARG 288 and halogen bond interaction with LYS 367. Further, PPAR gamma transactivation and gene expression studies of compound 6c were carried out to investigate the possible mechanism of action through PPAR gamma modulation. Compound 6c exhibited 53.65% transactivation and elevated PPAR gamma gene expression by 2.1 folds. The biochemical parameters (AST, ALT and ALP levels) were found within the range with no noteworthy damage to liver. (C) 2017 Elsevier Inc. All rights reserved.