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 4,7beta,17-trihydroxy-3,4-seco-28-norlup-20(29)-en-3-oic acid (5) and 7 beta,15 alpha-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.
Akihisa
Toshihiro
T
College of Science and Technology, Nihon University, 1-8 Kanda Surugadai, Chiyoda-ku, Tokyo 101-8308, Japan. akihisa@chem.cst.nihon-u.ac.jp
Takamine
Yoshio
Y
Yoshizumi
Kazuo
K
Tokuda
Harukuni
H
Kimura
Yumiko
Y
Ukiya
Motohiko
M
Nakahara
Toro
T
Yokochi
Toshihiro
T
Ichiishi
Eiichiro
E
Nishino
Hoyoku
H
D000956:Antigens, Viral / Q000187:drug effects; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D001711:Biotransformation; D004354:Drug Screening Assays, Antitumor; D005658:Fungi / Q000378:metabolism*; D006801:Humans; D007564:Japan; D016393:Lymphoma, B-Cell; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D009828:Oleanolic Acid / Q000031:analogs & derivatives / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D013237:Stereoisomerism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014315:Triterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D000094062:Betulinic Acid
D000956:Antigens, Viral; D000972:Antineoplastic Agents, Phytogenic; D009828:Oleanolic Acid; D013755:Tetradecanoylphorbol Acetate; D014315:Triterpenes; C033305:Epstein-Barr virus early antigen; C118308:betulonic acid; D000094062:Betulinic Acid; C002503:betulin