title: Effects of novel acylhydrazones derived from 4-quinolone on the acetylcholinesterase activity and Aβ42 peptide fibrils formation.
abstract: Acetylcholinesterase inhibitors and compounds that trigger Aβ amyloid oligomerization and fibrillization represent an opportunity to discover new drug candidates to treat Alzheimer's disease. In this work, we synthesized nine new acylhydrazones and a known one, both employing 3-carboethoxy-4-quinolone derivatives as starting materials with chemical yields ranging from 63% to 90%. We evaluated the effect of these compounds on the acetylcholinesterase (AChE) activity and the fibrillization of Aβ42 peptide. Except for one acylhydrazone, the compounds exhibited good inhibitory effect on AChE (1.2 μM < IC50 values < 17 μM). They also showed a significant decrease in the thioflavin-T fluorescence emission, suggesting an inhibitory effect on the Aβ42 fibril formation.
authors.affiliation: a Department of Organic Chemistry , Institute of Chemistry, University of Campinas , Campinas, São Paulo , Brazil and.
authors.forename: Gisele S
authors.initials: GS
authors.lastname: da Silva
authors.affiliation: b Faculty of Pharmaceutical Sciences , University of Campinas , Campinas, São Paulo , Brazil.
authors.forename: Micheli
authors.initials: M
authors.lastname: Figueiró
authors.affiliation: a Department of Organic Chemistry , Institute of Chemistry, University of Campinas , Campinas, São Paulo , Brazil and.
authors.forename: Claudio F
authors.initials: CF
authors.lastname: Tormena
authors.affiliation: a Department of Organic Chemistry , Institute of Chemistry, University of Campinas , Campinas, São Paulo , Brazil and.
authors.forename: Fernando
authors.initials: F
authors.lastname: Coelho
authors.affiliation: b Faculty of Pharmaceutical Sciences , University of Campinas , Campinas, São Paulo , Brazil.
authors.forename: Wanda P
authors.initials: WP
authors.lastname: Almeida
mesh_terms: D042462:4-Quinolones / Q000737:chemistry*; D000110:Acetylcholinesterase / Q000187:drug effects*; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000187:drug effects*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D006835:Hydrazones / Q000737:chemistry / Q000494:pharmacology*; D010446:Peptide Fragments / Q000737:chemistry / Q000187:drug effects*; D013057:Spectrum Analysis / Q000379:methods
chemical_list: D042462:4-Quinolones; D016229:Amyloid beta-Peptides; D002800:Cholinesterase Inhibitors; D006835:Hydrazones; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D000110:Acetylcholinesterase
keywords: Acetylcholinesterase; Alzheimer’s disease; acylhydrazone; quinolone; β-amyloid