Design, synthesis, and structure-activity relationship studies of novel millepachine derivatives as potent antiproliferative agents.
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.
State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Keyuan Road 4, Gaopeng Street, Chengdu 610041, China.
Guangcheng
G
Wang
Wenshuang
W
Wu
Fei
F
Peng
Dong
D
Cao
Zhuang
Z
Yang
Liang
L
Ma
Neng
N
Qiu
Haoyu
H
Ye
Xiaolei
X
Han
Jinying
J
Chen
Jingxiang
J
Qiu
Yun
Y
Sang
Xiaolin
X
Liang
Yan
Y
Ran
Aihua
A
Peng
Yuquan
Y
Wei
Lijuan
L
Chen
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001578:Benzopyrans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001688:Biological Products / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D050150:Chalones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D060326:Chemistry Techniques, Synthetic; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D001578:Benzopyrans; D001688:Biological Products; D050150:Chalones