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Library Construction and Biological Evaluation of Enmein‐Type Diterpenoid Analogues as Potential Anticancer Agents
Author(s) -
Li Dahong,
Xu Shengtao,
Cai Hao,
Pei Lingling,
Wang Lei,
Wu Xiaoming,
Yao Hequan,
Jiang Jieyun,
Sun Yijun,
Xu Jinyi
Publication year - 2013
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201200559
Subject(s) - terpenoid , chemistry , cancer , in vivo , pharmacology , cancer cell lines , stereochemistry , paclitaxel , apoptosis , in vitro , cancer cell , computational biology , combinatorial chemistry , biology , biochemistry , microbiology and biotechnology , genetics
Abstract A library of promising enmein‐type 14‐ O ‐diterpenoid derivatives was constructed from a commercially available kaurene‐type oridonin by practical and efficient synthetic methods. These synthetic derivatives were evaluated for their antiproliferative activities against a set of four human cancer cell lines. The IC 50 values are similar to or improved over those of the parent molecule and paclitaxel, the latter of which was used as a positive control. Compound 29 was further investigated for its apoptotic properties against human hepatocarcinoma Bel‐7402 cells to better understand its mode of action. Moreover, compound 29 was shown to have potent antitumor activity in vivo in studies with a murine model of gastric cancer (MGC‐803 mice). These results warrant further preclinical investigations of these diterpenoid‐based analogues as potential novel anticancer chemotherapeutics.