Synthesis and biological evaluation of novel triptolide analogues for anticancer activity

Bing Zhou; Zehong Miao; Gang Deng; Jian Ding; Yaxi Yang; Huijin Feng; Yuanchao Li

doi:10.1016/j.bmcl.2010.08.106

Synthesis and biological evaluation of novel triptolide analogues for anticancer activity

Bioorg Med Chem Lett. 2010 Nov 1;20(21):6217-21. doi: 10.1016/j.bmcl.2010.08.106. Epub 2010 Aug 26.

Authors

Bing Zhou¹, Zehong Miao, Gang Deng, Jian Ding, Yaxi Yang, Huijin Feng, Yuanchao Li

Affiliation

¹ Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Road Zu Chong Zhi, Zhangjiang Hi-Tech Park, Shanghai 201203, PR China.

PMID: 20833543
DOI: 10.1016/j.bmcl.2010.08.106

Abstract

Three types of novel triptolide analogues with 9,11-olefin (3-5), five-membered unsaturated lactam ring (6-7) or A/B cis ring junction (8-14) were synthesized. Although with 9,11-olefin instead of 9,11-β-epoxide, compound 4a was much more active than the parent natural triptolide (1) with the lowest IC(50) value of 0.05nM for SKOV-3 cells, clearly challenging the traditional viewpoint on the necessity of 9,11-β-epoxide group of triptolide. In addition, structure-activity relationships for three classes of compounds were studied.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents, Phytogenic / chemical synthesis*
Antineoplastic Agents, Phytogenic / pharmacology*
Cell Line, Tumor
Crystallography, X-Ray
Diterpenes / chemical synthesis*
Diterpenes / pharmacology*
Drug Screening Assays, Antitumor
Epoxy Compounds / chemical synthesis
Epoxy Compounds / pharmacology
Humans
Indicators and Reagents
Models, Molecular
Phenanthrenes / chemical synthesis*
Phenanthrenes / pharmacology*
Structure-Activity Relationship
Tripterygium / chemistry

Substances

Antineoplastic Agents, Phytogenic
Diterpenes
Epoxy Compounds
Indicators and Reagents
Phenanthrenes
triptolide