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Bioorg Med Chem Lett. 2014 Jul 15;24(14):3034-42. doi: 10.1016/j.bmcl.2014.05.034. Epub 2014 May 22.

Thiazolidine-2,4-diones derivatives as PPAR-γ agonists: synthesis, molecular docking, in vitro and in vivo antidiabetic activity with hepatotoxicity risk evaluation and effect on PPAR-γ gene expression.

Author information

1
Department of Chemistry, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi 110 062, India.
2
Department of Chemistry, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi 110 062, India. Electronic address: msalam5555@gmail.com.
3
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), New Delhi 110 062, India.
4
CSIR Unit for Research and Development of Information Products, Pune 411 038, India.
5
Functional Genomics Unit, CSIR-Institute of Genomics & Integrative Biology, New Delhi, India.
6
Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), New Delhi 110 062, India.

Abstract

A library of conjugates of chromones and 2,4-thiazolidinedione has been synthesized by Knoevenagel condensation followed by reduction using hydrogen gas and Pd/C as a catalyst. Compounds 5c and 5e were most effective in lowering the blood glucose level comparable to standard drug pioglitazone. Compound 5e exhibited potent PPAR-γ transactivation of 48.72% in comparison to pioglitazone (62.48%). All the molecules showed good glide score against the PPAR-γ target in molecular docking study. PPAR-γ gene expression was significantly increased by compound 5e (2.56-fold) in comparison to standard drug pioglitazone. Compounds 5e and 5c did not cause any damage to the liver and may be considered as promising candidates for the development of new antidiabetic agents.

KEYWORDS:

2,4-Thiazolidinedione; Antidiabetic activity; Chromone; Hepatotoxicity; PPAR-γ

PMID:
24890090
DOI:
10.1016/j.bmcl.2014.05.034
[Indexed for MEDLINE]

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