Structural modification of an angiogenesis inhibitor discovered from traditional Chinese medicine and a structure-activity relationship study.
Pseudolaric acid B (PAB), discovered as a promising angiogensis inhibitor, was served as the anticancer drug lead, and a series of its derivatives were synthesized. Among them, some derivatives, such as 13c- 13k, exhibited potent inhibition on the HMEC-1 cell proliferation and strong cytotoxic activities against the tested six tumor cell lines. The PAB derivatives 13c- 13k also showed significant and specific inhibition on HMEC-1 cell migration in vitro, and only 13d expressed moderate activity against HMEC-1 cell tube formation. The in vitro anticancer tests of the selected natural PAB analogs and the structurally modified PAB derivatives have led to the establishment of a clear structure-activity relationship.
Yang
Sheng-Ping
SP
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Zhangjiang Hi-Tech Park, Shanghai, 201203, People's Republic of China.
Cai
Yu-Jun
YJ
Zhang
Bang-Le
BL
Tong
Lin-Jiang
LJ
Xie
Hua
H
Wu
Yan
Y
Lin
Li-Ping
LP
Ding
Jian
J
Yue
Jian-Min
JM
D020533:Angiogenesis Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004224:Diterpenes / Q000737:chemistry* / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology; D042783:Endothelial Cells / Q000187:drug effects; D006801:Humans; D008833:Microcirculation / Q000166:cytology; D013329:Structure-Activity Relationship
D020533:Angiogenesis Inhibitors; D004224:Diterpenes; D004365:Drugs, Chinese Herbal; C058391:pseudolaric acid B