Synthesis and antiangiogenic activity of novel gambogic acid derivatives.
Gambogic acid (GA) is in a phase II clinical trial as an antitumor and antiangiogenesis agent. In this study, 36 GA derivatives were synthesized and screened in a zebrafish model to evaluate their antiangiogenic activity and toxicity. Derivatives 4, 32, 35, 36 effectively suppressed the formation of newly grown blood vessels and showed lower toxicities than GA as evaluated by zebrafish heart rates and mortalities. They also exhibited more potent migration and HUVEC tube formation inhibiting activities than GA. Among them, 36 was the most potent one, suggesting that it may serve as a potential new antiangiogenesis candidate with low toxicity. Additionally, 36 showed comparable antiproliferative activity to HUVECs and five tumor cell lines but low cytotoxicity to LO2 cells.
State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan 610041, China.
Tao
T
Chen
Rong-Hong
RH
Zhang
Shi-Chao
SC
He
Qin-Yuan
QY
Xu
Liang
L
Ma
Guang-Cheng
GC
Wang
Neng
N
Qiu
Fei
F
Peng
Jin-Ying
JY
Chen
Jing-Xiang
JX
Qiu
Ai-Hua
AH
Peng
Li-Juan
LJ
Chen
D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D030801:Animals, Genetically Modified; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004625:Embryo, Nonmammalian / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D018919:Neovascularization, Physiologic / Q000187:drug effects; D013329:Structure-Activity Relationship; D044004:Xanthones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015027:Zebrafish
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D044004:Xanthones; C052659:gambogic acid