title: Structure requirements for antiproliferative and cytotoxic activities of marine coral prostanoids from the Japanese stolonifer Clavularia viridis against human myeloid leukemia cells in culture.
abstract: The structural requirements for antiproliferative and cytotoxic activities of marine coral prostanoids from Japanese stolonifer Clavularia viridis and related compounds were examined in HL-60 cells in culture. From our data on the structure-activity relationship of these compounds, we elucidated that 1) the alkylidenecyclopentenone structure in these prostanoids was required for the antiproliferative and cytotoxic activities against HL-60 cells, but the epoxy prostanoids without cross-conjugated cyclopentenone system had the activities; 2) the presence of hydroxyl group at C-12 position in the prostanoids enhanced the activities, but the stereospecificity of the 12-hydroxyl group was not required for the activities; 3) the introduction of halogen atom at C-10 position of the prostanoids potentiated the activities (Cl greater than Br = I greater than H); 4) the introduction of blocking groups for blocking beta-oxidation to the alpha-side chain of the prostanoids did not cause the marked increase of the activities; 5) the presence of dienone (C5-6 and C7-8) in the structure potentiated the activities. These results provide the basis for drug-design of a new class of antitumor agent from marine coral prostanoids.
authors.affiliation: Department of Biochemistry, Tokyo College of Pharmacy, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Honda
authors.forename: Y
authors.initials: Y
authors.lastname: Mori
authors.forename: K
authors.initials: K
authors.lastname: Iguchi
authors.forename: Y
authors.initials: Y
authors.lastname: Yamada
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005227:Fatty Acids / Q000494:pharmacology*; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute; D008974:Mollusca; D011466:Prostanoic Acids / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D005227:Fatty Acids; D011466:Prostanoic Acids