Potential anti-tumor-promoting activity of 3α-hydroxy-D:A-friedooleanan-2-one from the stem bark of Mallotus philippensis

Four known friedelane-type triterpenoids, friedelin (1), 3-hydroxy-D:A-friedoolean-3-en-2-one (2), 20-hydroxy-D:A-friedooleanan-3-one (3), and 3 alpha-hydroxy-D:A-friedooleanan-2-one (4), and two known lupane-type triterpenoids, lupeol (5) and betulin (6), were isolated from the stem bark of Mallotus philippensis. Isolates 1-4 and their synthetic analogues, 3-acetoxy-D:A-friedoolean-3-en-2-one (2a) and 3 alpha-acetoxy-D:A-friedooleanan-2-one (4a), were tested for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol 13-acetate (TPA). The inhibitory effect of compounds 2 (IC50 = 292 mol ratio/32 pmol/TPA) and 4 (IC50=288) was stronger than those of the other compounds tested and the positive control, curcumin (IC50=343). Compound 4 strongly inhibited mouse skin tumor promotion in an in vivo two-stage carcinogenesis model. Studies have been conducted to identify the biologically active compounds extracted from the leaves, bark, and cones of trees that currently have no specific commercial use and are therefore treated as waste in the forestry industry.