Anti-tumor promoting diterpenes from the stem bark of Thuja standishii (Cupressaceae).

Abstract

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.

• Authors: M Iwamoto, H Ohtsu, H Tokuda, H Nishino, S Matsunaga, R Tanaka
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 9 Issue 7 Pg. 1911-21 (Jul 2001) ISSN: 0968-0896 [Print] England
• PMID: 11425594 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents, Phytogenic
• Carcinogens
• Diterpenes
• 9,10-Dimethyl-1,2-benzanthracene
• Tetradecanoylphorbol Acetate

Topics

• 9,10-Dimethyl-1,2-benzanthracene (toxicity)
• Animals
• Antineoplastic Agents, Phytogenic (pharmacology)
• Carcinogens (toxicity)
• Diterpenes (pharmacology)
• Female
• Mice
• Mice, Inbred ICR
• Plant Stems (chemistry)
• Skin Neoplasms (chemically induced, prevention & control)
• Tetradecanoylphorbol Acetate (toxicity)
• Trees (chemistry)