The conversion of oridonin to spirolactone-type or enmein-type diterpenoid: Synthesis and biological evaluation of ent-6,7-seco-oridonin derivatives as novel potential anticancer agents

Lei Wang, Dahong Li, Shengtao Xu, Hao Cai, Hequan Yao, Yihua Zhang, Jieyun Jiang, Jinyi Xu

Research output: Contribution to journalArticlepeer-review

63 Scopus citations

Abstract

Starting from commercial available natural product oridonin (1), a practical synthesis of ent-6,7-seco-oridonin derivatives (2, 3, 5, and 9) was accomplished and their biological activities were evaluated. The conversion of spirolactone-type diterpenoid to enmein-type was first completed. The results demonstrated that all synthesized ent-6,7-seco-oridonin derivatives could markedly inhibit the proliferation of cancer cells. Compared with Taxol, the most cytotoxic compound 5 has similar potency in A549 cell and slightly less cytotoxicity in Bel-7402 cell. Compound 5 was also more potent than parent compound oridonin in mice with MGC-803 gastric cancer in vivo. Then a series of novel 14-O-derivatives of 5 were further designed and synthesized, which showed better activity than 5 and similar activity as Taxol in vitro. The structure-activity relationships of oridonin derivatives were also discussed in the present investigations.

Original languageEnglish
Pages (from-to)242-250
Number of pages9
JournalEuropean Journal of Medicinal Chemistry
Volume52
DOIs
StatePublished - Jun 2012

Bibliographical note

Funding Information:
This study was supported by grant from National Natural Science Fund (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 (2011, No. 800), the Fundamental Research Funds for the Central Universities ( JKY2011030 ) and Key Fund of Ministry of Education of China (No. 108069 ) for financial assistance.

Keywords

  • Anti-tumor activity
  • Cytotoxicity
  • Enmein-type diterpenoid
  • Spirolactone-type diterpenoid
  • Structure-activity relationship
  • ent-6,7-seco-Oridonin derivatives

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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