Synthesis of neuroprotective cyclopentenone prostaglandin analogs: suppression of manganese-induced apoptosis of PC12 cells |
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| Authors: | Furuta Kyoji Maeda Masahide Hirata Yoko Shibata Shoko Kiuchi Kazutoshi Suzuki Masaaki |
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| Institution: | Regeneration and Advanced Medical Science, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu 501-1194, Japan. |
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| Abstract: | 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. |
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