Synthesis of neuroprotective cyclopentenone prostaglandin analogs: suppression of manganese-induced apoptosis of PC12 cells.
The synthesis and evaluation for anti- and proapoptotic properties of cyclopentenone prostaglandin analogs are described. Novel J-type analogs of NEPP11 with a cross-conjugated cyclopentadienone moiety and a lipophilic omega-side chain suppressed manganese ion-induced apoptosis of PC12 cells at comparable levels to NEPP11, while monoenone derivatives were inactive. The proapoptotic activities of J-type analogs were much lower than that of NEPP11. Natural 15-deoxy-Delta(12,14)-PGJ(2) and Delta(7)-PGA(1) methyl ester were highly toxic, inducing apoptosis at lower concentrations.
Furuta
Kyoji
K
Regeneration and Advanced Medical Science, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu 501-1194, Japan.
Maeda
Masahide
M
Hirata
Yoko
Y
Shibata
Shoko
S
Kiuchi
Kazutoshi
K
Suzuki
Masaaki
M
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053938:DNA Fragmentation / Q000187:drug effects; D007202:Indicators and Reagents; D008345:Manganese / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D016716:PC12 Cells; D011465:Prostaglandins, Synthetic / Q000138:chemical synthesis* / Q000494:pharmacology*; D051381:Rats
D007202:Indicators and Reagents; D018696:Neuroprotective Agents; D011465:Prostaglandins, Synthetic; D008345:Manganese