The synthesis of 18beta-glycyrrhetinic acid derivatives which have increased antiproliferative and apoptotic effects in leukemia cells.
18beta-Glycyrrhetinic acid (GA), 3beta-hydroxyl-11-oxo-olean-12-ene-29-oic acid, has been found to inhibit growth and to induce apoptosis in cancer cells. Through structural modification, 16 GA derivatives (12 novel compounds) with modified structures at the C(3) and C(29) positions were synthesized. The antiproliferative effects and apoptosis induction abilities of these compounds were determined in human leukemia HL-60 cells. The replacement of the hydroxyl group of GA with a carbonyl group or an oxime group at C(3) position does not influence the antiproliferative effect. However, the antiproliferative and apoptosis induction abilities of the compounds with a replaced alkoxyimino group at position C(3) and a free C(29) carboxyl group are markedly increased.
Liu
Dan
D
Shenyang Pharmaceutical University, Shenyang 110016, PR China.
Song
Dandan
D
Guo
Gang
G
Wang
Rui
R
Lv
Jinling
J
Jing
Yongkui
Y
Zhao
Linxiang
L
D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D018922:HL-60 Cells; D006801:Humans; D007938:Leukemia / Q000473:pathology*; D015394:Molecular Structure
D006034:Glycyrrhetinic Acid