| Literature DB >> 28582649 |
Mohd Javed Naim1, Md Jahangir Alam1, Farah Nawaz1, V G M Naidu2, Shams Aaghaz3, Meeta Sahu1, Nadeem Siddiqui1, Ozair Alam4.
Abstract
A series of thiazolidinedione based amide derivatives were designed, synthesized and docked against the PPARγ 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, PPARγ transactivation and gene expression studies of compound 6c were carried out to investigate the possible mechanism of action through PPARγ modulation. Compound 6c exhibited 53.65% transactivation and elevated PPARγ 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.Entities:
Keywords: Antidiabetic; Molecular docking; PPARγ; Thiazolidinedione
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Year: 2017 PMID： 28582649 DOI： 10.1016/j.bioorg.2017.05.007
Source DB: PubMed Journal: Bioorg Chem ISSN： 0045-2068 Impact factor: 5.275