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

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• 作者：Guangcheng Wang^a ; ¹ ; Wenshuang Wu^a ; ¹ ; Fei Peng^a ; Dong Cao^a ; Zhuang Yang^a ; ^b ; Liang Ma^a ; Neng Qiu^a ; Haoyu Ye^a ; Xiaolei Han^a ; Jinying Chen^a ; Jingxiang Qiu^a ; Yun Sang^a ; ^b ; Xiaolin Liang^a ; Yan Ran^a ; ^c ; Aihua Peng^a ; Yuquan Wei^a ; Lijuan Chen^a ; ^{Lijuan170@hotmail.com}
• 关键词：Millepachine ; Chalcone ; Tubulin ; Antiproliferative activity ; Cell cycle arrest ; Anticancer activity
• 刊名：European Journal of Medicinal Chemistry
• 出版年：2012
• 出版时间：August, 2012
• 年：2012
• 卷：54
• 期：Complete
• 页码：793-803
• 全文大小：1235 K

文摘

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 IC₅₀?=?0.64 vs. 2.86?¦ÌM, 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.