Syntheses, neural protective activities, and inhibition of glycogen synthase kinase-3β of substituted quinolines.
Basic Information
ID: ALA3352531
Journal: Bioorg Med Chem Lett
Title: Syntheses, neural protective activities, and inhibition of glycogen synthase kinase-3β of substituted quinolines.
Authors: Lu J, Maezawa I, Weerasekara S, Erenler R, Nguyen TD, Nguyen J, Swisher LZ, Li J, Jin LW, Ranjan A, Srivastava SK, Hua DH.
Abstract: A new series of fifteen 5-, 6-, and 8-appended 4-methylquinolines were synthesized and evaluated for their neural protective activities. Selected compounds were further examined for their inhibition of glycogen synthase kinase-3β (GSK-3β) and protein kinase C (PKC). Two most potent analogs, compounds 3 and 10, show nanomolar protective activities in amyloid β-induced MC65 cells and enzymatic inhibitory activities against GSK-3β, but poor PKC inhibitory activities. Using normal mouse model, the distribution of the most potent analog 3 in various tissues and possible toxic effects in the locomotors and inhibition of liver transaminases activities were carried out. No apparent decline of locomotor activity and no inhibition of liver transaminases were found. The compound appears to be safe for long-term use in Alzheimer's disease mouse model.
CiteXplore: 24951331
DOI: 10.1016/j.bmcl.2014.05.085
Patent ID: ┄