Design, synthesis, and structure-activity relationship studies of novel millepachine derivatives as potent antiproliferative agents

  • Eur J Med Chem. 2012 Aug:54:793-803. doi: 10.1016/j.ejmech.2012.06.034.
Guangcheng Wang  1 ,  Wenshuang Wu ,  Fei Peng ,  Dong Cao ,  Zhuang Yang ,  Liang Ma ,  Neng Qiu ,  Haoyu Ye ,  Xiaolei Han ,  Jinying Chen ,  Jingxiang Qiu ,  Yun Sang ,  Xiaolin Liang ,  Yan Ran ,  Aihua Peng ,  Yuquan Wei ,  Lijuan Chen
Affiliations
  • 1. State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Keyuan Road 4, Gaopeng Street, Chengdu 610041, China.
PMID: 22784822 DOI: 10.1016/j.ejmech.2012.06.034
Abstract

In this paper, 38 millepachine derivatives have been designed, synthesized and evaluated for their in vitro and in vivo antiproliferative activity. Among these novel derivatives, 15 displayed more potent antiproliferative activity than millepachine against HepG2, K562, SK-OV-3, HCT116, HT29, and SW620 tumor cells (mean IC(50) = 0.64 vs. 2.86 μM, respectively). Furthermore, 15 could effectively inhibit tubulin polymerization in HepG2 cells, and induce the HepG2 cell cycle arrest at the G2/M phase in a concentration-dependant manner. Further studies confirmed that 15 significantly suppressed the growth of tumor volume and exerted more potent Anticancer potency than millepachine and Anticancer drug cisplatin in A549 lung xenograft tumor model.