Hybrids of coumarin–indole: design, synthesis and biological evaluation in Triton WR-1339 and high-fat diet induced hyperlipidemic rat models12. Issue 9 (26th July 2016)

• Record Type: Journal Article
• Authors: Sashidhara, Koneni V.; Rao, K. Bhaskara; Sonkar, Ravi; Modukuri, Ram K.; Chhonker, Yashpal S.; Kushwaha, Pragati; Chandasana, Hardik; Khanna, A. K.; Bhatta, Rabi S.; Bhatia, Gitika; Suthar, Manish Kumar; Saxena, Jitendra Kumar; Kumar, Vikash; Siddiqi, Mohammad Imran
• Is Part Of: MedChemComm. Volume 7:Issue 9(2016:Sep.)
• Page Start: 1858
• Page End: 1869
• Publication Date: 2016-07-26
• Subjects: Pharmaceutical chemistry -- Periodicals; 615.19
• DOI: 10.1039/c6md00283h
• Languages: English
• ISSNs: 2040-2503

Abstract

Abstract : Lipid lowering activity of novel coumarin–indole hybrids has been demonstrated. Abstract : In this study, a series of coumarin–indole hybrids have been synthesized and evaluated for their lipid lowering activity. Preliminary biological screening of the synthesized compounds was undertaken in an in vitro model of the HMG-CoA reductase enzyme, and the activity was confirmed in Triton WR-1339 induced hyperlipidemic rats. Among the hybrids, compound26 was found to be the best as it significantly reduced the serum and hepatic lipid profiles in an HFD-fed hyperlipidemic rat model. The mechanism of action seems to be associated with the regulation of HMG-CoA reductase activity in the liver, which is in good agreement with binding mode studies. Compound26 exhibited favorable pharmacokinetic behavior for its oral administration, which underscores the potential of this template as a new class of hypolipidemic agents.