Synthesis, Antitumor Activity And Structure-Activity Relationship Of25-methoxyprotopanaxadiol Derivatives

20(R)-25-methoxydammarane-3β,12β,20-triol (25-OCH3-PPD) is a dammarane-type sapogenin showing antitumor potential. In our study, two series of analogues substituted at the C(3) position or/and C(12) with fatty acids were prepared conveniently and determined in vitro by standard MTT assay using four different human tumor cell lines(A549, Hela, HT-29and MCF-7) and a normal cell line(IOSE144). As compared with25-OCH3-PPD, compounds1a,1c,2a,2c showed better antitumor activities against all tumor cell lines and all the derivatives with low toxicity in the normal cell line. The results indicated that differences in the substituent affect their antitumor activity and the rule is:the longer the side chain of25-OCH3-PPD is, the lower the antitumor activity is. This information may be useful for evaluating the structure-activity relationship of other dammarane-type sapogenins and for development of novel antineoplasticagents.