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 ω-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-Δ12,14-PGJ2 and Δ7-PGA1 methyl ester were highly toxic, inducing apoptosis at lower concentrations.