A series of enmein-type diterpenoid analogs (11-20) derived from natural kaurene-type diterpenoid oridonin were synthesized and biologically evaluated. All target compounds showed improved anti-proliferative activities against four human cancer cell lines compared with natural oridonin and parent compound 10. Some compounds were more potent than positive control Taxol. Furthermore, mechanistic investigation showed that the representative compound 17 affected cell cycle and induced apoptosis at low micro-molar level in human hepatoma Bel-7402 cells, via an oxidative stress triggered mitochondria-related caspase-dependent pathway.
|Number of pages||7|
|Journal||European Journal of Medicinal Chemistry|
|State||Published - 2013|
Bibliographical noteFunding Information:
This study was supported by a grant from the National Natural Science Foundation (No. 30973610 ), Specialized Research Fund for the Doctoral Program of Higher Education (No. 20100096110001 ), Project for Research and Innovation of Graduates in Universities of Jiangsu Province ( CXZZ11-0800 ), the Fundamental Research Funds for the Central Universities ( JKY2011030 ) and Key Fund of Ministry of Education of China (No. 108069 ) for financial assistance.
- Anti-proliferative activity
- Cell cycle analysis
- Enmein-type diterpenoid
ASJC Scopus subject areas
- Drug Discovery
- Organic Chemistry