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

• Published in: Bioorganic & medicinal chemistry Vol. 15; no. 16; pp. 5432 - 5439
• Main Authors: Liu, Dan, Song, Dandan, Guo, Gang, Wang, Rui, Lv, Jinling, Jing, Yongkui, Zhao, Linxiang
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 15.08.2007; Elsevier Science
• Subjects: 18β-Glycyrrhetinic acid; Antineoplastic agents; Apoptosis; Biological and medical sciences; General aspects; Medical sciences; Pharmacology. Drug treatments; Structure–activity relationship; Synthesis; 18β-Glycyrrhetinic acid; Synthesis; Structure–activity relationship; Apoptosis; Antineoplastic agent; Human; Terpenoid; Growth; Leukemia; Oxime; Malignant hemopathy; Enoxolone; In vitro; HL60 cell line; Dose activity relation; Oleanane derivatives; Cell line; Structure activity relation; Structure- activity relationship; Triterpene; Inhibition; Chemical synthesis; Tumor cell
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2007.05.057

18β-Glycyrrhetinic acid (GA), 3β-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.