Structure requirements for antiproliferative and cytotoxic activities of marine coral prostanoids from the Japanese stolonifer Clavularia viridis against human myeloid leukemia cells in culture.
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.
Honda
A
A
Department of Biochemistry, Tokyo College of Pharmacy, Japan.
Mori
Y
Y
Iguchi
K
K
Yamada
Y
Y
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*
D000970:Antineoplastic Agents; D005227:Fatty Acids; D011466:Prostanoic Acids