title: Structure-activity relationship within a series of okadaic acid derivatives.
abstract: Okadaic acid (OA) is a potent non-12-O-tetradecanoyl-phorbol-13-acetate (non-TPA) type tumor promoter on mouse skin. OA acts on cells through inhibiting the activity of protein phosphatases and results in the increase of phosphorylation of proteins. Seventeen OA derivatives were evaluated as possible tumor promoters by means of three biochemical tests: inhibition of specific [3H]OA binding to a particulate fraction of mouse skin containing protein phosphatases, inhibition of protein phosphatase activity, and induction of ornithine decarboxylase in mouse skin. Potency in each of these biochemical tests correlated well for each of these derivatives. We present results indicating that the carboxyl group as well as the four hydroxyl groups at C-2, C-7, C-24 and C-27 of OA are important for activity. Acanthifolicin, which gave positive responses in these three biochemical tests as strong as those of OA and dinophysistoxin-1, is predicted to be an additional member of the OA class of tumor promoters.
authors.affiliation: Cancer Prevention Division, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Nishiwaki
authors.forename: H
authors.initials: H
authors.lastname: Fujiki
authors.forename: M
authors.initials: M
authors.lastname: Suganuma
authors.forename: H
authors.initials: H
authors.lastname: Furuya-Suguri
authors.forename: R
authors.initials: R
authors.lastname: Matsushima
authors.forename: Y
authors.initials: Y
authors.lastname: Iida
authors.forename: M
authors.initials: M
authors.lastname: Ojika
authors.forename: K
authors.initials: K
authors.lastname: Yamada
authors.forename: D
authors.initials: D
authors.lastname: Uemura
authors.forename: T
authors.initials: T
authors.lastname: Yasumoto
mesh_terms: D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000201:enzymology; D002273:Carcinogens / Q000494:pharmacology*; D004988:Ethers, Cyclic / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D051379:Mice; D019319:Okadaic Acid; D009955:Ornithine Decarboxylase / Q000096:biosynthesis; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors; D012867:Skin / Q000187:drug effects / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D002273:Carcinogens; D004988:Ethers, Cyclic; D019319:Okadaic Acid; D010749:Phosphoprotein Phosphatases; D009955:Ornithine Decarboxylase