Anti-tumor promoting diterpenes from the stem bark of Thuja standishii (Cupressaceae).
Three new labdane-type diterpenoids, labda-8(17),13-dien-15,12R-olid-19-oic acid (1), 12S-hydroxylabda-8(17),13(16),14-trien-19-oic acid (2) and 13-ethoxylabda-8(17),11,14-trien-19-oic acid (3), along with known diterpenoids, trans-communic acid (4), totarol (5), 12-methoxyabieta-8,11,13-trien-11-ol (6), and 7 alpha,8 alpha-epoxy-6 alpha-hydroxyabieta-9(11),13-dien-12-one (7) were isolated from the stem bark of Thuja standishii. The structures of 1--3 were established by spectroscopic methods and chemical conversion. These compounds together with standishinal (8), 12-hydroxy-6,7-seco-abieta-8,11,13-trien-6,7-dial (9) and 6 alpha-hydroxysugiol (10) were tested for their inhibitory effects on Epstein--Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA), as a test for potential cancer chemopreventive agents. Compound 10 showed strong inhibitory effect on EBV-EA induction (100% inhibition at 1000 mol ratio/TPA), and compounds 2 and 6 showed moderate inhibitory effects on EBV-EA induction. In addition, 15-oxolabda-8(17),11Z,13E-trien-19-oic acid (11) was found to exhibit the anti-tumor promoting activity in two-stage mouse skin carcinogenesis test using 7,12-dimethylbenz[a]anthracene and TPA.
Iwamoto
M
M
Department of Medicinal Chemistry, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
Ohtsu
H
H
Tokuda
H
H
Nishino
H
H
Matsunaga
S
S
Tanaka
R
R
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002273:Carcinogens / Q000633:toxicity; D004224:Diterpenes / Q000494:pharmacology*; D005260:Female; D051379:Mice; D008813:Mice, Inbred ICR; D018547:Plant Stems / Q000737:chemistry; D012878:Skin Neoplasms / Q000139:chemically induced / Q000517:prevention & control; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity; D014197:Trees / Q000737:chemistry*
D000972:Antineoplastic Agents, Phytogenic; D002273:Carcinogens; D004224:Diterpenes; D015127:9,10-Dimethyl-1,2-benzanthracene; D013755:Tetradecanoylphorbol Acetate