Open AccessPendolmycin, a New Tumor Promoter of the Teleocidin A Class on Skin of CD‐1 Mice
Author(s) -
Nishiwaki Shinji,
Fujiki Hirota,
Yoshizawa Seiji,
Suganuma Masami,
FuruyaSuguri Hiroko,
Okabe Sachiko,
Nakayasu Michie,
Okabe Kazuaki,
Muratake Hideaki,
Natsume Mitsutaka,
Umezawa Kazuo,
Sakai Shinichiro,
Sugimura Takashi
Publication year - 1991
Publication title -
japanese journal of cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 0910-5050
DOI - 10.1111/j.1349-7006.1991.tb02702.x
Subject(s) - moiety , stereochemistry , tetradecanoylphorbol acetate , biochemistry , chemistry , structure–activity relationship , anticarcinogen , biological activity , in vitro , kinase , protein kinase c
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 C 5 dimethyl allyl group attached to C‐7 of (‐)‐indolactam‐V, whereas teleocidin A has a C 10 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 [ 3 H]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.