Synthesis and evaluation of cytotoxic effects of novel α-methylenelactone tetracyclic diterpenoids

Yao-Fu Zeng; Jia-Qiang Wu; Lian-Yong Shi; Ke Wang; Bin Zhou; Yong Tang; Da-Yong Zhang; Yang-Chang Wu; Wei-Yi Hua; Xiao-Ming Wu

doi:10.1016/j.bmcl.2012.01.051

Synthesis and evaluation of cytotoxic effects of novel α-methylenelactone tetracyclic diterpenoids

Bioorg Med Chem Lett. 2012 Mar 1;22(5):1922-5. doi: 10.1016/j.bmcl.2012.01.051. Epub 2012 Jan 26.

Authors

Yao-Fu Zeng¹, Jia-Qiang Wu, Lian-Yong Shi, Ke Wang, Bin Zhou, Yong Tang, Da-Yong Zhang, Yang-Chang Wu, Wei-Yi Hua, Xiao-Ming Wu

Affiliation

¹ Center of Drug Discovery, College of Pharmacy, China Pharmaceutical University, 24 Road Tongjia Xiang, Nanjing 210009, China.

PMID: 22318158
DOI: 10.1016/j.bmcl.2012.01.051

Abstract

A series of tetracyclic diterpenoids bearing the α-methylenelactone group have been synthesized and screened for their in vitro anti-tumor activities against six human cancer cell lines. The results showed that compounds 1c, 2a and 2b exhibited significant cytotoxicity superior to the positive control doxorubicin hydrochloride against MDA-MB-231, K562 and HepG2 cell lines. In particular, compound 2b was identified as the most promising anticancer agent against HepG2 cells with IC(50) value of 0.09μM.

Publication types

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

MeSH terms

Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry*
Antineoplastic Agents / pharmacology*
Cell Line, Tumor
Cell Survival / drug effects
Diterpenes / chemical synthesis
Diterpenes / chemistry*
Diterpenes / pharmacology*
Humans
Lactones / chemical synthesis
Lactones / chemistry*
Lactones / pharmacology*
Neoplasms / drug therapy
Structure-Activity Relationship

Substances

Antineoplastic Agents
Diterpenes
Lactones
methylene-lactone