Journal
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
Volume 64, Issue -, Pages 215-221Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2013.04.012
Keywords
Enmein-type diterpenoid; Oridonin; Anti-proliferative activity; Cell cycle analysis; Apoptosis
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Funding
- National Natural Science Foundation [30973610]
- Specialized Research Fund for the Doctoral Program of Higher Education [20100096110001]
- Project for Research and Innovation of Graduates in Universities of Jiangsu Province [CXZZ11-0800]
- Fundamental Research Funds for the Central Universities [JKY2011030]
- Ministry of Education of China [108069]
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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. (C) 2013 Elsevier Masson SAS. All rights reserved.
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