Semi-synthesis Of (20S)-Protopanaxadiol Derivatives And Screening For In Vitro Antitumor Activities

(20S)-Protopanaxadiol, one of important metabolites from natural ginseng saponins in vivo, exhibits significant anti-tumor activities. Functionalization of 3-,12-, and 20-hydroxyl groups of (20S)-protopanaxadiol produced 15 derivatives bearing alkyloxy group, carbonyl group, oxime group, or amino group.(20S,24R)-empridamarane-3,12,25-triol is a metabolite of (20S)-protopanaxadiol in human hepatocytes which exhibited good antitumor activity. Starting from (20S,24R)-empridamarane-3,12,25-triol, the three hydroxyl groups are further coverted into other functional groups, such as alkyloxy, carbonyl, or amino group. Then another 12 derivatives are obtained. The structures of these derivatives have been confirmed by 1H NMR and ESI-MS.Totally 27 derivatives are involved in anti-tumor activity tests in vitro using four cells by MTT method. The four cells are A549 human lung adenocarcinoma cell lines, 7721 liver cancer cell lines, A375 human melanoma cell lines and human HL60 leukemia cell lines. Three semi-synthesized derivatives exhibit good anti-tumor activities with the IC50 lower than 1 μM.