Pendolmycin, a new tumor promoter of the teleocidin A class on skin of CD-1 mice.

Abstract

Pendolmycin, isolated from Nocardiopsis, is a compound structurally similar to teleocidin A, one of the 12-O-tetradecanoylphorbol-13-acetate (TPA)-type tumor promoters. Pendolmycin has a C5 dimethyl allyl group attached to C-7 of (-)-indolactam-V, whereas teleocidin A has a C10 linalyl group attached to the molecule. The structure-activity relationships of a hydrophobic moiety attached to (-)-indolactam-V were studied in four compounds, (-)-indolactam-V, pendolmycin, teleocidin A and newly synthesized 7-(nerolidyl)-(-)-indolactam-V in tests on inhibition of the specific [3H]TPA binding to a particulate fraction of mouse skin, activation of protein kinase C and induction of both adhesion of HL-60 cells and ornithine decarboxylase in mouse skin. The potencies of the compounds for these activities increased mainly depending on the length of the hydrophobic group. Pendolmycin had a tumor-promoting activity on mouse skin initiated with a single application of 7,12-dimethyl-benz[a]anthracene, and its potency was just between those of (-)-indolactam-V and teleocidin A. The role of the hydrophobic moiety is discussed with particular emphasis on the results obtained with 7-(nerolidyl)-(-)-indolactam-V.

• Authors: S Nishiwaki, H Fujiki, S Yoshizawa, M Suganuma, H Furuya-Suguri, S Okabe, M Nakayasu, K Okabe, H Muratake, M Natsume
• Journal: Japanese journal of cancer research : Gann (Jpn J Cancer Res) Vol. 82 Issue 7 Pg. 779-83 (Jul 1991) ISSN: 0910-5050 [Print] Japan
• PMID: 1908844 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Alkaloids
• Carcinogens
• Indoles
• Lactams
• Lyngbya Toxins
• Tritium
• pendolmycin
• indolactam V
• Protein Kinase C
• Tetradecanoylphorbol Acetate
• lyngbyatoxin A

Topics

• Alkaloids (toxicity)
• Animals
• Carcinogens (toxicity)
• Enzyme Activation
• Female
• Indoles (toxicity)
• Lactams (toxicity)
• Lyngbya Toxins (toxicity)
• Mice
• Mice, Inbred Strains
• Protein Kinase C (drug effects, metabolism)
• Skin (drug effects, metabolism)
• Skin Neoplasms (chemically induced)
• Structure-Activity Relationship
• Tetradecanoylphorbol Acetate (metabolism)
• Tritium