Microbial transformation of isosteviol and inhibitory effects on Epstein-Barr virus activation of the transformation products.
Microbial transformation of isosteviol (2), a beyerane-type diterpenoid obtained from stevioside (1) by acid hydrolysis, yielded 7beta-hydroxyisosteviol (3), 11beta-hydroxyisosteviol (5), and 12beta-hydroxyisosteviol (6) by the fungus Aspergillus niger, 17-hydroxyisosteviol (7) by the fungus Glomerella cingulata, and 3 and 7-oxoisosteviol (4) by the fungus Mortierella elongate. The five metabolites, 3-7, 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 promoters. All the diterpenes tested showed potent inhibitory effects, with the five metabolites 3-7 exhibiting more potent effects.
Akihisa
Toshihiro
T
College of Science and Technology, Nihon University, 1-8 Kanda Surugdai, Chiyoda-ku, Tokyo 101-8308, Japan. akihisa@chem.cst.nihon-u.ac.jp
Hamasaki
Yusuke
Y
Tokuda
Harukuni
H
Ukiya
Motohiko
M
Kimura
Yumiko
Y
Nishino
Hoyoku
H
D000956:Antigens, Viral / Q000187:drug effects; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology; D001711:Biotransformation; D004224:Diterpenes / Q000737:chemistry* / Q000494:pharmacology; D045786:Diterpenes, Kaurane; D004305:Dose-Response Relationship, Drug; D005960:Glucosides / Q000737:chemistry / Q000494:pharmacology; D004854:Herpesvirus 4, Human / Q000502:physiology; D006801:Humans; D020094:Mortierella / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014775:Virus Activation
D000956:Antigens, Viral; D000972:Antineoplastic Agents, Phytogenic; D004224:Diterpenes; D045786:Diterpenes, Kaurane; C033305:Epstein-Barr virus early antigen; D005960:Glucosides; C012043:stevioside; C012042:steviol; D013755:Tetradecanoylphorbol Acetate