Structure-activity studies on synthetic analogues (indolactams) of the tumor promoter teleocidin.
Synthetic analogues (indolactams) related to the tumor promoter teleocidin were synthesized chemically. Of four indolactam-Vs lacking the monoterpenoid moiety of native teleocidin, (-)-indolactam-V bound to the 12-O-tetradecanoylphorbol-13-acetate receptor in cell membranes and induced both adhesion of HL-60 cells and ornithine decarboxylase activity in mouse skin, although its effects were weaker than those of teleocidin. (+)-Indolactam-V and two isomers of epi-indolactam-V showed no induction of ornithine decarboxylase. These results indicate that the S,S configuration of native teleocidin at the isopropyl residue and the hydroxymethyl group is necessary for activity.
D000818:Animals; D029742:Caenorhabditis elegans Proteins; D002273:Carcinogens / Q000494:pharmacology*; D002352:Carrier Proteins; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D004790:Enzyme Induction; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D007700:Kinetics; D007769:Lactams / Q000494:pharmacology*; D015470:Leukemia, Myeloid, Acute; D051379:Mice; D009955:Ornithine Decarboxylase / Q000096:biosynthesis; D011493:Protein Kinase C; D011955:Receptors, Drug; D011971:Receptors, Immunologic / Q000187:drug effects / Q000378:metabolism; D012867:Skin / Q000201:enzymology; D013329:Structure-Activity Relationship; D013755:Tetradecanoylphorbol Acetate / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; D002273:Carcinogens; D002352:Carrier Proteins; D007211:Indoles; D007769:Lactams; D011955:Receptors, Drug; D011971:Receptors, Immunologic; C083141:phorbol ester binding protein; C027776:phorbol ester receptor; C043969:indolactam V; D011493:Protein Kinase C; D009955:Ornithine Decarboxylase; D013755:Tetradecanoylphorbol Acetate