title: Syntheses, neural protective activities, and inhibition of glycogen synthase kinase-3β of substituted quinolines.
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.
authors.affiliation: Department of Chemistry, 213 CBC Building, Kansas State University, Manhattan, KS 66506, United States.
authors.forename: Jianyu
authors.initials: J
authors.lastname: Lu
authors.affiliation: M.I.N.D. Institute and Department of Pathology, 2825 50th Street, UC Davis Health System, Sacramento, CA 95817, United States.
authors.forename: Izumi
authors.initials: I
authors.lastname: Maezawa
authors.affiliation: Department of Chemistry, 213 CBC Building, Kansas State University, Manhattan, KS 66506, United States.
authors.forename: Sahani
authors.initials: S
authors.lastname: Weerasekara
authors.affiliation: Department of Chemistry, 213 CBC Building, Kansas State University, Manhattan, KS 66506, United States.
authors.forename: Ramazan
authors.initials: R
authors.lastname: Erenler
authors.affiliation: Department of Chemistry, 213 CBC Building, Kansas State University, Manhattan, KS 66506, United States.
authors.forename: Tuyen D T
authors.initials: TD
authors.lastname: Nguyen
authors.affiliation: Department of Chemistry, 213 CBC Building, Kansas State University, Manhattan, KS 66506, United States.
authors.forename: James
authors.initials: J
authors.lastname: Nguyen
authors.affiliation: Department of Chemistry, 213 CBC Building, Kansas State University, Manhattan, KS 66506, United States.
authors.forename: Luxi Z
authors.initials: LZ
authors.lastname: Swisher
authors.affiliation: Department of Chemistry, 213 CBC Building, Kansas State University, Manhattan, KS 66506, United States.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: M.I.N.D. Institute and Department of Pathology, 2825 50th Street, UC Davis Health System, Sacramento, CA 95817, United States.
authors.forename: Lee-Way
authors.initials: LW
authors.lastname: Jin
authors.affiliation: Department of Biomedical Sciences and Cancer Biology Center, Texas Tech University Health Sciences Center, Amarillo, TX 79106, United States.
authors.forename: Alok
authors.initials: A
authors.lastname: Ranjan
authors.affiliation: Department of Biomedical Sciences and Cancer Biology Center, Texas Tech University Health Sciences Center, Amarillo, TX 79106, United States.
authors.forename: Sanjay K
authors.initials: SK
authors.lastname: Srivastava
authors.affiliation: Department of Chemistry, 213 CBC Building, Kansas State University, Manhattan, KS 66506, United States. Electronic address: duy@ksu.edu.
authors.forename: Duy H
authors.initials: DH
authors.lastname: Hua
mesh_terms: D000544:Alzheimer Disease / Q000201:enzymology* / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051379:Mice; D023421:Models, Animal; D015394:Molecular Structure; D011493:Protein Kinase C / Q000378:metabolism; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D011804:Quinolines; D011493:Protein Kinase C; D038362:Glycogen Synthase Kinase 3
keywords: Alzheimer’s disease; Amyloid β; Glycogen synthase kinase-3β; Neural protective activity; Protein kinase C; Quinolines