Semi-synthesis And Anti-tumor Evaluation Of Novel25-hydroxyprotopanaxadiol Derivatives

25-hydroxyprotopanaxadiol (20(R)-dammarane-3β,12β,20,25-tetrol,25-OH-PPD) was a novel natural product isolated from fi-uits of panax ginseng and had stronger antitumor effect than ginsenoside-Rg3(Shenyijiaonang, an agent already being marketed for cancer therapy). In vitro and in vivo studies demonstrated that25-OH-PPD inhibited proliferation, caused cell cycle arrest, the growth of xenograft tumors without obvious host toxicity and induced apoptosis.25-OH-PPD was separated by silica gel column chromatography from the hydrolyzate of notoginsenoside and the structure was determined via chemical and physical methods. Previous pharmacokinetic studies have demonstrated that the fatty acid esterification of ginsenoside possibly represented a detoxification reaction in the body. To confirm whether the theory is adequate for25-OH-PPD and find more potent, higher selectivity compounds, series of derivatives were synthesized and their antitumor activities were evaluated in the present study. Finally30kinds of esterfication products were obtained and idantified as:(20R)-12β,20,25-trihydroxydammarane-3B-yl formiate (1),(20R)-12β,20,25-trihydroxydammarane-3β-yl acetate (2),(20R)-12β,20,25-trihydroxydammarane-3β-yl propionate (3),(20R)-12β,20,25-trihydroxydammarane-3β-yl butyrate (4),(20R)-12β,20,25-trihydroxydammarane-3β-yl valerate (5),(20R)-12β,20,25-trihydroxydammarane-3β-yl caproate (6),(20R)-12B,20,25-trihydroxydammarane-3B-yl heptanoate (7),(20R)-12β,20,25-trihydroxydammarane-3β-yl octoate (8),(20R)-12β,20,25-trihydroxydammarane-3β-yl pelargonate (9),(20R)-12β,20,25-trihydroxydammarane-3β-yl caprate (10),(20R)-12β,20,25-trihydroxydammarane-3β-yl laurate (11),(20R)-12β,20,25-trihydroxydammarane-3β-yl myristinate (12),(20R)-12β,20,25-trihydroxydammarane-3β-yl palmitate (13),(20R)-12β,20,25-trihydroxydammarane-3β-yl stearate (14),.(20R)-12β,20,25-trihydroxydammarane-3β-yl oleate (15),(20R)-3β,20,25-trihydroxydammarane-12β-yl formiate (16),(20R)-3β,20,25-trihydroxydammarane-12B-yl acetate (17),(20R)-3β,20,25-trihydroxydammarane-12β-yl propionate (18),(20R)-3β,20,25-trihydroxydammarane-12β-yl butyrate (19),(20R)-3β,20,25-trihydroxydammarane-12β-yl heptanoate (20),(20R)-3β,20,25-trihydroxydammarane-12β-yl caprate (21),(20R)-3β,20,25-trihydroxydammarane-12β-yl laurate (22),(20R)-3β,20,25-trihydroxydammarane-12β-yl myristinate (23),(20R)-3β,20,25-trihydroxydammarane-12β-yl palmitate (24),(20R)-3β,20,25-trihydroxydammarane-12β-yl stearate (25),(20R)-3β,20,25-trihydroxydammarane-12β-yl oleate (26),(20R)-20,25-dihydroxydammarane-3β,12β-yl formiate (27),(20R)-20,25-dihydroxydammarane-3β,12β-yl acetate (28),(20R)-20,25-dihydroxydammarane-3β,12β-yl propionate (29),(20R)-20,25-dihydroxydammarane-3β,12β-yl valerate (30).30novel compounds have been synthesized from25-OH-PPD and their in vitro anti-tumor activities were tested on human breast cancer MCF-7cells, human lung cancer A549cells, human colorectal cancer Lovo cells and human ovarian surface epithelial IOSE144cells by standard MTT assay. The results showed that compound27exhibited the best anti-tumor activity in the in vitro assays. Compounds1,2,16,17,18,27,28and29have better anti-tumor activities against MCF-7and A549cancer cell lines than25-OH-PPD, together with low toxicity in the normal cell. The results may provide useful data for researching and developing new anti-cancer agents.