title: 25-Methoxylprotopanaxadiol derivatives and their anti-proliferative activities.
abstract: (20R)-25-Methoxyl-dammarane-3β,12β,20-triol (25-OCH₃-PPD) is a dammarane-type sapogenin showing anti-proliferative potential. In our study, two series of analogs substituted at the C-3 or C-3 and C-12 positions with fatty acids were prepared conveniently. The cytotoxic activity of these compounds was evaluated using four different human tumor cell lines (A549, Hela, HT-29 and MCF-7) and a normal cell line (IOSE144). As compared with 25-OCH₃-PPD, compounds 1a, 1b, 2a and 2b showed better anti-proliferative activities against all tumor cell lines and all the derivatives, with low toxicities in the normal cell line. Compound 1a (C-3 monoformiate) exhibited the strongest activity with the IC₅₀ value of 5.2 μM towards HT29 cells. The results indicated that the difference in the substituents may affect the anti-proliferative activity of the compounds. The longer the side chain of 25-OCH₃-PPD is, the lower the anti-proliferative activity would be. This information may be useful for evaluating the structure-activity relationship of other dammarane-type sapogenins and for development of novel antineoplastic agents.
authors.affiliation: School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
authors.forename: Ya-Fei
authors.initials: YF
authors.lastname: Liu
authors.forename: Hao-Nan
authors.initials: HN
authors.lastname: Yuan
authors.forename: Xiu-Li
authors.initials: XL
authors.lastname: Bi
authors.forename: Hu-Ri
authors.initials: HR
authors.lastname: Piao
authors.forename: Jia-Qing
authors.initials: JQ
authors.lastname: Cao
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.forename: Yu-Qing
authors.initials: YQ
authors.lastname: Zhao
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D036145:Ginsenosides / Q000737:chemistry*; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D012502:Sapogenins / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000737:chemistry*; D000097669:Dammaranes
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D036145:Ginsenosides; D012502:Sapogenins; D014315:Triterpenes; D000097669:Dammaranes; C062916:protopanaxadiol
keywords: 25-OCH(3)-PPD; Anti-proliferative; Derivatives; MTT; Structure–activity relationship