title: Design, synthesis, and evaluation of guanylhydrazones as potential inhibitors or reactivators of acetylcholinesterase.
abstract: Analogs of pralidoxime, which is a commercial antidote for intoxication from neurotoxic organophosphorus compounds, were designed, synthesized, characterized, and tested as potential inhibitors or reactivators of acetylcholinesterase (AChE) using the Ellman's test, nuclear magnetic resonance, and molecular modeling. These analogs include 1-methylpyridine-2-carboxaldehyde hydrazone, 1-methylpyridine-2-carboxaldehyde guanylhydrazone, and six other guanylhydrazones obtained from different benzaldehydes. The results indicate that all compounds are weak AChE reactivators but relatively good AChE inhibitors. The most effective AChE inhibitor discovered was the guanylhydrazone derived from 2,4-dinitrobenzaldehyde and was compared with tacrine, displaying similar activity to this reference material. These results indicate that guanylhydrazones as well as future similar derivatives may function as drugs for the treatment of Alzheimer's disease.
authors.affiliation: a Department of Chemistry , Military Institute of Engineering , Rio De Janeiro , Brazil .
authors.forename: Elaine da Conceição
authors.initials: Eda C
authors.lastname: Petronilho
authors.affiliation: b Laboratory of Molecular Modeling and Pharmaceutical Sciences , Federal University of Rio De Janeiro , Macaé , Brazil , and .
authors.forename: Magdalena do Nascimento
authors.initials: Mdo N
authors.lastname: Rennó
authors.affiliation: c Institute of Biomedical Sciences , Federal University of Rio De Janeiro , Rio De Janeiro , Brazil.
authors.forename: Newton Gonçalves
authors.initials: NG
authors.lastname: Castro
authors.affiliation: c Institute of Biomedical Sciences , Federal University of Rio De Janeiro , Rio De Janeiro , Brazil.
authors.forename: Fernanda Motta R
authors.initials: FM
authors.lastname: da Silva
authors.affiliation: a Department of Chemistry , Military Institute of Engineering , Rio De Janeiro , Brazil .
authors.forename: Angelo da Cunha
authors.initials: Ada C
authors.lastname: Pinto
authors.affiliation: a Department of Chemistry , Military Institute of Engineering , Rio De Janeiro , Brazil .
authors.forename: José Daniel
authors.initials: JD
authors.lastname: Figueroa-Villar
mesh_terms: D000110:Acetylcholinesterase / Q000187:drug effects*; D066241:Carbon-13 Magnetic Resonance Spectroscopy; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D002801:Cholinesterase Reactivators / Q000737:chemistry* / Q000494:pharmacology*; D004793:Enzyme Reactivators / Q000494:pharmacology*; D006835:Hydrazones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D066244:Proton Magnetic Resonance Spectroscopy; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D004793:Enzyme Reactivators; D006835:Hydrazones; D000110:Acetylcholinesterase
keywords: Acetylcholinesterase; Alzheimer’s disease; NMR plus Ellman’s test; guanylhydrazones; molecular docking