The synthesis of ursolic acid derivatives with cytotoxic activity and the investigation of their preliminary mechanism of action.
Nineteen ursolic acid derivatives (15 novel compounds) modified at the C-3 and the C-28 positions were synthesized. The cytotoxic activity of the derivatives was evaluated against HeLa, BGC-823 and SKOV3 cells by MTT assay. Inducing apoptosis and affecting cell cycle distribution by the derivatives in HeLa cells were assessed by flow cytometry and DNA fragmentation. Compounds 10b and 11b were particularly active to inhibit HeLa cells growth through inducing apoptosis and arresting cell cycle progression. The typical 'sub-G1 peak' and DNA ladder formation were checked and cell cycle was arrested at the S phase in a dose-dependent manner.
Meng
Yan-Qiu
YQ
Department of Pharmaceutical Engineering, Shenyang Institute of Chemical Technology, Jing Ji Kai Fa Que 11 street, Shenyang 110142, PR China. mengyanqiu@hotmail.com
Liu
Dan
D
Cai
Ling-Li
LL
Chen
Hong
H
Cao
Bo
B
Wang
Yi-Zheng
YZ
D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation; D006801:Humans; D014315:Triterpenes / Q000138:chemical synthesis* / Q000494:pharmacology; D000097245:Ursolic Acid
D000972:Antineoplastic Agents, Phytogenic; D014315:Triterpenes; D000097245:Ursolic Acid