Cucurbitane Triterpenoids from the Leaves of Momordica charantia, and Their Cancer Chemopreventive Effects and Cytotoxicities

Seventeen cucurbitane-type triterpenoids, 117, including six new compounds, (23E)-3 beta,25-dihydroxy-7 beta-methoxycucurbita-5,23-dien-19-al (1), (23S*)-3 beta-hydroxy-7 beta,23-dimethoxycucurbita-5,24-dien-19-al (6), (23R*)-23-O-methylmomordicine IV (7), (25?)-26-hydroxymomordicoside L (8), 25-oxo-27-normomordicoside L (9), and 25-O-methylkaravilagenin D (12), were isolated from a MeOH extract of the leaves of Japanese Momordica charantia. The structures of new compounds were elucidated on the basis of extensive spectroscopic analyses and comparison with literature. Compounds 117 were examined for their inhibitory effects on Epstein?Barr virus early antigen (EBV-EA) activation induced with 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells, a known primary screening test for inhibitors of tumor promotion. Four compounds, 1, (23E)-3 beta,7 beta-dihydroxy-25-methoxycucurbita-5,23-dien-19-al (2), karavilagenin D (11), and 12, showed potent inhibitory effects on EBV-EA induction with IC50 values in the range of 242264 mol ratio/32 pmol TPA. In addition, compounds 1 and 11 exhibited inhibitory effects on skin-tumor promotion in an in vivo two-stage mouse skin carcinogenesis test based on 7,12-dimethylbenz[a]anthracene (DMBA) as initiator, and with TPA as a promoter. Furthermore, upon evaluation of the cytotoxic activities of compounds 117 against human cancer cell lines, compounds 2, 57, 9, and 14 showed potent activities against HL60 cell line, and compound 2 against SK-BR-3 cell line.