Synthesis, biological evaluation and in silico and in vitro mode-of-action analysis of novel dihydropyrimidones targeting PPAR-y
| dc.contributor.author | Bharathkumar, H. | |
| dc.contributor.author | Paricharak, S. | |
| dc.contributor.author | Dinesh, K. | |
| dc.contributor.author | Siveen, S. | |
| dc.contributor.author | Fuchs, J. | |
| dc.contributor.author | Rangappa, S. | |
| dc.contributor.author | Mohan, C. | |
| dc.contributor.author | Mohandas, N. | |
| dc.contributor.author | Kumar, Alan Prem | |
| dc.contributor.author | Sethi, G. | |
| dc.contributor.author | Bender, A. | |
| dc.contributor.author | Basappa | |
| dc.contributor.author | Rangappa, K. | |
| dc.date.accessioned | 2017-01-30T13:02:57Z | |
| dc.date.available | 2017-01-30T13:02:57Z | |
| dc.date.created | 2015-03-19T20:00:17Z | |
| dc.date.issued | 2014 | |
| dc.identifier.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. | |
| dc.identifier.uri | http://hdl.handle.net/20.500.11937/28077 | |
| dc.identifier.doi | 10.1039/c4ra08713e | |
| dc.description.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. | |
| dc.publisher | Royal Society of Chemistry | |
| dc.title | Synthesis, biological evaluation and in silico and in vitro mode-of-action analysis of novel dihydropyrimidones targeting PPAR-y | |
| dc.type | Journal Article | |
| dcterms.source.volume | 4 | |
| dcterms.source.startPage | 45143 | |
| dcterms.source.endPage | 45146 | |
| dcterms.source.issn | 2046-2069 | |
| dcterms.source.title | RSC Advances | |
| curtin.department | School of Biomedical Sciences | |
| curtin.accessStatus | Open access via publisher |