Relationship between ornithine decarboxylase-inducing activity and configuration at C-4 in phorbol ester derivatives.
Measurements were made of induction of ornithine decarboxylase activity after painting mouse skin with 12-O-hexadecanoyl-16-hydroxyphorbol-13-acetate and its two epimeric 4-deoxy-analogs, 12-O-hexadecanoyl-4-deoxy-16-hydroxyphorbol-13-acetate and 12-O-hexadecanoyl-4-deoxy-4 alpha-16-hydroxyphorbol-13 acetate. The inductive activities of HHPA and 4-deoxy-HHPA were similar, but 4-deoxy-4 alpha HHPA had no inductive activity. These findings on natural phorbol esters confirm that both the 4 beta-hydrogen and the 4 beta-hydroxyl in phorbol esters are essential for ODC-inducing activity. The interactions of 4-deoxy-HHPA and 4-deoxy-4 alpha-HHPA with a possible receptor are discussed.
D000818:Animals; D002262:Carboxy-Lyases / Q000096:biosynthesis*; D055598:Chemical Phenomena; D002621:Chemistry; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D051379:Mice; D009955:Ornithine Decarboxylase / Q000096:biosynthesis*; D010703:Phorbol Esters / Q000494:pharmacology*; D010704:Phorbols / Q000494:pharmacology*; D012867:Skin / Q000187:drug effects / Q000201:enzymology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D010703:Phorbol Esters; D010704:Phorbols; C028113:croton factor F1; C028114:croton factor F2; C028115:12-O-hexadecanoyl-4-deoxy-4 alpha-16-hydroxyphorbol-13-acetate; D002262:Carboxy-Lyases; D009955:Ornithine Decarboxylase