Microbial Transformations of Two Lupane-Type Triterpenes and Anti-Tumor-Promoting Effects of the Transformation Products

Microbial transformation of betulin (1), a lupane-type triterpene obtained from the bark extract of white birch (Betula platyphylla Sukatshev var. japonica), and its chemical oxidation product, betulonic acid (2), by the fungus Chaetomium longirostre yielded 4,28-dihydroxy-3,4-seco-lup-20(29)-en-3-oic acid (3) and 4-hydroxy-3,4-seco-lup-20(29)-ene-3,28-dioic acid (4) from 1, and 4,7β,17-trihydroxy-3,4-seco-28-norlup-20(29)-en-3-oic acid (5) and 7β,15α-dihydoxy-3-oxolup-20(29)-en-28-oic acid (6) from 2. The four metabolites, 3−6, along with 1 and 2, were evaluated for their inhibitory effects on Epstein−Barr virus early antigen (EBV-EA) activation induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells as a primary screening test for inhibitors of tumor promotion. All of the triterpenes tested showed potent inhibitory effects, with the four metabolites 3−6 exhibiting the more potent effects.