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

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Hanumantharayappa Bharathkumar, . and Shardul Paricharak, . and Dinesh, K.R. and Kodappully Sivaraman Siveen, . and Julian, E.Fuchs. and Shobith Rangappa, . and Mohan, C.D. and Nima Mohandas, . and Alan Prem Kumar, . and Gautam Sethi, . and Andreas Bender, . 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-gamma. RSC Advances, 04. 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 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 mu M), being at the same time 7.6-fold selective over normal (LO2) liver cells (IC50 = 136.9 mu M). Subsequently, we identified peroxisome proliferator-activated receptor gamma as a target of compound 4g using an in silico approach, and confirmed this mode-of-action experimentally.

Item Type: Article
Uncontrolled Keywords: ACTIVATED RECEPTOR-GAMMA; BREAST-CANCER CELLS; AGONISTS; INHIBIT; J(2); IDENTIFICATION; LIGANDS; MICE
Subjects: Faculty of Science > Pure Sciences > Chemistry
Divisions: Jnana Bharathi / Central College Campus > Department of Chemistry
Depositing User: Mr H.G. Srikanth
Date Deposited: 24 Oct 2016 07:01
Last Modified: 24 Oct 2016 07:01
URI: http://eprints-bangaloreuniversity.in/id/eprint/6871

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