Synthesis, biological evaluation and in silico and in vitro mode-of-action analysis of novel dihydropyrimidones targeting PPAR-Y

Bharathkumar, H. and Paricharak, S. and Dinesh, K. R. and Siveen, K. S. and Fuchs, J. E. and Rangappa, S. and Mohan, C. D. and Mohandas, N. and Prem Kumar, A. and Sethi, G. and Bender, A. and Basappa and Rangappa, K. S. (2014) Synthesis, biological evaluation and in silico and in vitro mode-of-action analysis of novel dihydropyrimidones targeting PPAR-Y. RSC Advances, 4 (85). pp. 45143-45146. ISSN 2046-2069

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Official URL: https://doi.org/10.1039/c4ra08713e

Abstract

Hepatocellular carcinoma, a fatal liver cancer, affects 600000 people annually and ranks third in cancer-related lethality. In this work we report the synthesis and related biological activity of novel dihydropyrimidones. Among the tested compounds, 5-acetyl-4-(1H-indol-3-yl)-6-methyl-3,4-dihydropyrimidin-2(1H)-one (4g) was found to be most active towards the HepG2 cell line (IC50= 17.9 μM), being at the same time 7.6-fold selective over normal (LO2) liver cells (IC50= 136.9 μM). Subsequently, we identified peroxisome proliferator-activated receptor γ as a target of compound 4g using an in silico approach, and confirmed this mode-of-action experimentally.

Item Type: Article
Uncontrolled Keywords: In-vitro, Biological evaluation, In-silico
Subjects: C Chemical Science > Chemistry
Divisions: Department of > Chemistry
Depositing User: Arshiya Kousar
Date Deposited: 15 Jun 2019 07:33
Last Modified: 10 Jul 2019 05:30
URI: http://eprints.uni-mysore.ac.in/id/eprint/3080

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