Nobuko Sakurai

Antitumor agents 220. Antitumor-promoting effects of cimigenol and related compounds on Epstein-Barr virus activation and two-stage mouse skin carcinogenesis.

Cimigenol (1) and 39 related compounds were screened as potential antitumor promoters by examining the ability of the compounds to inhibit Epstein-Barr virus early antigen (EBV-EA) activation (induced by 12-O-tetradecanoylphorbol-13-acetate) in Raji cells. Structure-activity relationship analysis indicated that compound 1 showed the highest activity and also exhibited significant inhibitory effects on mouse skin tumor promotion in an in vivo two-stage carcinogenesis test. These data suggest that 1 and the related compounds might be valuable anti-tumor promoters.

Acetyl Shengmanol, a Possible Parental Triterpene Acetate of Cimigenol and Cimigol from Cimicifuga japonica

A new triterpene glycoside (I) named acetyl shengmanol xyloside, mp 280-281°, [α]27D-23.7°, which was isolated from the underground part of Gimicifga japonica, yielded an amorphous aglycone (XII) on enzymatic hydrolysis. The peracetate of I afforded mainly 25-O-methylcimigenol (IV) along with cimigenol (V) and isodahurinol (VI) on acidic hydrolysis, while I gave cimigol xyloside (III), mp 297-299°, on alkaline treatment. The degradation of I with meta-periodate-cyclohexylamine gave an aldehyde-carboxylic acid, methyl ester of which has structure (IX). From chemical and spectral evidence, the structure of acetyl shengmanol (XII) was proposed to be (23R, 24S)-24, 25-epoxy-3β, 15ξ-dihydroxy-23-acetoxy-9, 19-cyclolanost-16-one. I is so unstable that it is readily convertible to cimigol xyloside (III) on alkaline treatment and to cimigenol (V) during acid hydrolysis. XII seems to be a precursor of cimigenol and cimigol in C. japonica. The mechanism of transformation of XII to V and VII was discussed.