The cytotoxic activity of ursolic acid derivatives.
Ursolic acid and 2alpha-hydroxyursolic acid isolated from apple peels were found to show growth inhibitory activity against four tumor cell lines, HL-60, BGC, Bel-7402 and Hela. Structural modifications were performed on the C-3, C-28 and C-11 positions of ursolic acid and the cytotoxicity of the derivatives was evaluated. The SAR revealed that the triterpenes possessing two hydrogen-bond forming groups (an H-donor and a carbonyl group) at positions 3 and 28 exhibit cytotoxic activity. The configuration at C-3 was found to be important for the activity. Introduction of an amino group increased the cytotoxicity greatly. A 3beta-amino derivative was 20 times more potent than the parent ursolic acid. The 28-aminoalkyl dimer compounds showed selective cytotoxicity.
Ma
Chao-Mei
CM
School of Pharmaceutical Sciences, Peking University, No. 38 Xueyuan Road, Haidian District, Beijing 100083, China.
Cai
Shao-Qing
SQ
Cui
Jing-Rong
JR
Wang
Rui-Qing
RQ
Tu
Peng-Fei
PF
Hattori
Masao
M
Daneshtalab
Mohsen
M
D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D018922:HL-60 Cells; D006367:HeLa Cells; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D027845:Malus / Q000737:chemistry; D015394:Molecular Structure; D012235:Rhodamines / Q000737:chemistry; D014315:Triterpenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000097245:Ursolic Acid
D000972:Antineoplastic Agents, Phytogenic; D012235:Rhodamines; D014315:Triterpenes; D000097245:Ursolic Acid; C022027:lissamine rhodamine B