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Issue 85, 2014
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Synthesis, biological evaluation and in silico and in vitro mode-of-action analysis of novel dihydropyrimidones targeting PPAR-γ

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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

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Publication details

The article was received on 15 Aug 2014, accepted on 02 Sep 2014 and first published on 02 Sep 2014


Article type: Communication
DOI: 10.1039/C4RA08713E
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Citation: RSC Adv., 2014,4, 45143-45146
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    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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