Synthesis, biological evaluation and in silico and in vitro mode-of-action analysis of novel dihydropyrimidones targeting PPAR-y
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-dihydropy...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Journal Article |
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Royal Society of Chemistry
2014
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| Online Access: | http://hdl.handle.net/20.500.11937/28077 |
| _version_ | 1848752438755983360 |
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| author | 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. |
| author_facet | 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. |
| author_sort | Bharathkumar, H. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T08:08:38Z |
| format | Journal Article |
| id | curtin-20.500.11937-28077 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T08:08:38Z |
| publishDate | 2014 |
| publisher | Royal Society of Chemistry |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-280772017-09-13T15:13:27Z 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. 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. 2014 Journal Article http://hdl.handle.net/20.500.11937/28077 10.1039/c4ra08713e Royal Society of Chemistry unknown |
| spellingShingle | 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. Synthesis, biological evaluation and in silico and in vitro mode-of-action analysis of novel dihydropyrimidones targeting PPAR-y |
| title | Synthesis, biological evaluation and in silico and in vitro mode-of-action analysis of novel dihydropyrimidones targeting PPAR-y |
| title_full | Synthesis, biological evaluation and in silico and in vitro mode-of-action analysis of novel dihydropyrimidones targeting PPAR-y |
| title_fullStr | Synthesis, biological evaluation and in silico and in vitro mode-of-action analysis of novel dihydropyrimidones targeting PPAR-y |
| title_full_unstemmed | Synthesis, biological evaluation and in silico and in vitro mode-of-action analysis of novel dihydropyrimidones targeting PPAR-y |
| title_short | Synthesis, biological evaluation and in silico and in vitro mode-of-action analysis of novel dihydropyrimidones targeting PPAR-y |
| title_sort | synthesis, biological evaluation and in silico and in vitro mode-of-action analysis of novel dihydropyrimidones targeting ppar-y |
| url | http://hdl.handle.net/20.500.11937/28077 |