Issue 85, 2014

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

Abstract

Hepatocellular carcinoma, a fatal liver cancer, affects 600 000 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.

Graphical abstract: Synthesis, biological evaluation and in silico and in vitro mode-of-action analysis of novel dihydropyrimidones targeting PPAR-γ

Supplementary files

Article information

Article type
Communication
Submitted
15 Aug 2014
Accepted
02 Sep 2014
First published
02 Sep 2014
This article is Open Access
Creative Commons BY license

RSC Adv., 2014,4, 45143-45146

Author version available

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

H. Bharathkumar, S. Paricharak, K. R. Dinesh, K. S. Siveen, J. E. Fuchs, S. Rangappa, C. D. Mohan, N. Mohandas, A. P. Kumar, G. Sethi, A. Bender, Basappa and K. S. Rangappa, RSC Adv., 2014, 4, 45143 DOI: 10.1039/C4RA08713E

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