Designed cyclopentenone prostaglandin derivatives as neurite outgrowth-promoting compounds for CAD cells, a rat catecholaminergic neuronal cell line of the central nervous system.
Here we reported the effects of neurite outgrowth-promoting prostaglandins (NEPP's) on neurons of the central nervous system (CNS). Serum deprivation promoted neurite outgrowth from CAD cells, a CNS-derived cathecholaminergic neuronal cell line. NEPP's (0.05-0.2 microM) accelerated the neurite outgrowth from CAD cells in serum-free medium but didn't in serum-containing medium. Through the study of structure-function relationship with the NEPP's 1-10, NEPP 10 (13,14-dihydro-15-epi-Delta(7)-prostaglandin A(1) (methyl ester) revealed the best compound, exhibiting potent neurite outgrowth-promoting activity with minimal cytotoxicity, suggesting that it is the best compound for drug development.
Satoh
T
T
Department of Neuroscience, Osaka Bioscience Institute, Suita-shi, 565-0874, Osaka, Japan. tsatoh@obi.or.jp
Furuta
K
K
Tomokiyo
K
K
Suzuki
M
M
Watanabe
Y
Y
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003517:Cyclopentanes / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D016501:Neurites / Q000187:drug effects*; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011454:Prostaglandins A / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship; D013778:Tetrazolium Salts; D013844:Thiazoles
C416053:13,14-dihydro-delta7-prostaglandin A1 methyl ester; D003517:Cyclopentanes; D011454:Prostaglandins A; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue; C013905:cyclopentenone