The synthesis of 18β-glycyrrhetinic acid derivatives which have increased antiproliferative and apoptotic effects in leukemia cells

18 beta-Glycyrrhetinic acid (GA), 3 beta-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. (c) 2007 Elsevier Ltd. All rights reserved.