Synthesis of spirolactone-type diterpenoid derivatives from kaurene-type oridonin with improved antiproliferative effects and their apoptosis-inducing activity in human hepatoma Bel-7402 cells.

A series of novel spirolactone-type diterpenoid derivatives of oridonin (12a-j) were designed and synthesized. All the target compounds showed improved anti-proliferative activity against a panel of human cancer cell lines and the most effective compound 12j was more potent than positive control Taxol in K562 and Bel-7402 cells with IC(50) values of 0.39 μM and 1.39 μM, respectively. The cellular mechanisms showed that compound 12j induced apoptosis at low micromolar concentrations in human hepatoma Bel-7402 cells. These results demonstrate that the spirolactone-type diterpenoid derivatives of oridonin have optimized growth inhibitory activity against cancer cells and interesting apoptosis-inducing ability.
AuthorsDahong Li, Hao Cai, Bowen Jiang, Guyue Liu, Yuetong Wang, Lei Wang, Hequan Yao, Xiaoming Wu, Yijun Sun, Jinyi Xu
JournalEuropean journal of medicinal chemistry (Eur J Med Chem) Vol. 59 Pg. 322-8 (Jan 2013) ISSN: 1768-3254 [Electronic] France
PMID23274570 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2012 Elsevier Masson SAS. All rights reserved.
Chemical References
  • Antineoplastic Agents
  • Diterpenes
  • Diterpenes, Kaurane
  • oridonin
  • Spironolactone
  • kaurene
  • Paclitaxel
  • Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
  • Apoptosis (drug effects)
  • Cell Cycle (drug effects)
  • Cell Line, Tumor
  • Diterpenes (chemical synthesis, chemistry, pharmacology)
  • Diterpenes, Kaurane (chemical synthesis, chemistry, pharmacology)
  • Flow Cytometry
  • Humans
  • Inhibitory Concentration 50
  • Liver Neoplasms (drug therapy)
  • Models, Molecular
  • Paclitaxel (therapeutic use)
  • Spironolactone (chemical synthesis, chemistry, pharmacology)

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