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

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.

doi:10.1039/c4ra08713e

Access Status

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

2014

Type

Journal Article

Metadata

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Citation

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

DOI

10.1039/c4ra08713e

ISSN

2046-2069

School

School of Biomedical Sciences

URI

http://hdl.handle.net/20.500.11937/28077

Collection

Curtin Research Publications

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.