Pendolmycin, a new tumor promoter of the teleocidin A class on skin of CD-1 mice.
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.
Nishiwaki
S
S
Cancer Prevention Division, National Cancer Center Research Institute, Tokyo.
Fujiki
H
H
Yoshizawa
S
S
Suganuma
M
M
Furuya-Suguri
H
H
Okabe
S
S
Nakayasu
M
M
Okabe
K
K
Muratake
H
H
Natsume
M
M
D000470:Alkaloids / Q000633:toxicity*; D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D004789:Enzyme Activation; D005260:Female; D007211:Indoles / Q000633:toxicity; D007769:Lactams / Q000633:toxicity; D008235:Lyngbya Toxins / Q000633:toxicity; D051379:Mice; D008815:Mice, Inbred Strains; D011493:Protein Kinase C / Q000187:drug effects / Q000378:metabolism; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D012878:Skin Neoplasms / Q000139:chemically induced*; D013329:Structure-Activity Relationship; D013755:Tetradecanoylphorbol Acetate / Q000378:metabolism; D014316:Tritium
D000470:Alkaloids; D002273:Carcinogens; D007211:Indoles; D007769:Lactams; D008235:Lyngbya Toxins; D014316:Tritium; C059313:pendolmycin; C043969:indolactam V; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; C019457:lyngbyatoxin A