Studies On Semi-Synthesis Of Some Rare Ginsenosides And Structure-Function Relationship In Antitumor Activity

Ginseng (Panax ginseng C.A. Meyer) has been used as a drug by the people in the Eastern Asia regions for 2000 yr. It is generally believed that the major bioactive components of ginseng are the ginsenosides. Over 30 different ginsenosides have been isolated and structures determined. Specifically,ginsenoside Rg3,Rh2 and compound CK, have been reported to posses bioactivity in alter cancer cell proliferation, induce apoptosis, and perturb normal cell cycle events, shown potential clinical value in cancer therapy. In order to search for new antitumor ginsenosides and prepare samples for structure-function relationship study, difference hydrolysis ways were investigated: (1). 50% acetic acid hydrolysis of total ginsenoside was reviewed, the result shown that ginsenosides changed into various sub-ginsenosides and their epimer. (2). 20(S)-Protopanaxadiol and 20(S)-protopanaxatriol changed into epimer 20(R)-propanaxadiol and 20(R)- protopanaxatriol under acid and H2O2. Fourteen sub-ginsenosides were isolated from hydrolysis ways for ginsenoside by silica gel chromatography. Their structures were elucidated by spectroscopic methods, including, MS and NMR: 20(S)-protopanaxatriol (1), 20(S)-protopanaxadiol (2), 20(S)-protopanaxadiol-3-O-beta-D-glucopyr-anoside (3), 20(R)-protopanaxadiol-3-O-beta-D-glucopyranoside(4), 20(S)-protopanaxadiol-3-O- beta-D-glucopyranosyl(1,2)-beta-D-glucopyranoside (5), 20(R)-protopanaxadiol-3-O -beta-D-glucoyranosyl(1,2)-beta-D-glucopyranoside (6), 20(R)-protopanaxatriol (7), 20(R)-protopanaxadiol (8), 20(S)-panaxadiol (9), 20(S)-panaxatriol (10), 20(R)-panaxadiol (11), 20(R)-panaxatriol (12), 20-O-(beta-D-glucopyranosy)-20(S)- protopanaxadiol (13), 20(S)-protopanaxadiol-20-O-a-L-arabinofuranosyl(1,6) –beta- D-glucopyranoside(14). Semi-synthesis of some rare ginsenosides industrial methods were established, including alkali hydrolysis prepare 20(S)-protopanaxadiol and 20(S)-protopanaxatriol, Enzymatic translation for preparation ginsenoside CK. Fourteen sub-ginsenosides, together with five commonly ginsenoside, Rb1, Rb3, Rg1, Re and Rd, were screened for antitumor activity against four human tumor cell lines A-2780, HCT-8, SMMC-7721 and PC-3M. In the in vitro activity test, most of sub-ginsenosides exhibited strong antitumor activity. Especially IC50 value of 20(S)-protopanaxadiol was found to be 3.45, 5.13, 2.13 and 6.08μg/ml against four human tumor cell lines A-2780, HCT-8, SMMC-7721 and PC-3M respectively. Five commonly ginsenoside, Rb1, Rb3, Rg1, Re and Rd do not show antitumor activity. Comparing various Structure with function relationship in antitumor of ginsenosides, the results shown that protopanaxadiol classification had stronger antitumor activity than protopanaxatriol classification, 20(S)-type sub-ginsenosides was stronger than 20(R)-type in antitumor activity.