Synthesis, biological evaluation and in silico and in vitro mode-of-action analysis of novel dihydropyrimidones targeting PPAR-y
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Open access via publisher
Authors
Bharathkumar, H.
Paricharak, S.
Dinesh, K.
Siveen, S.
Fuchs, J.
Rangappa, S.
Mohan, C.
Mohandas, N.
Kumar, Alan Prem
Sethi, G.
Bender, A.
Basappa
Rangappa, K.
Date
2014Type
Journal Article
Metadata
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Bharathkumar, H. and Paricharak, S. and Dinesh, K. and Siveen, S. and Fuchs, J. and Rangappa, S. and Mohan, C. et al. 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.
Source Title
RSC Advances
ISSN
School
School of Biomedical Sciences
Collection
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.