title: Alkaloid metabolite profiles by GC/MS and acetylcholinesterase inhibitory activities with binding-mode predictions of five Amaryllidaceae plants.
abstract: Acetylcholinesterase (AChE) enzymatic inhibition is an important target for the management of Alzheimer disease (AD) and AChE inhibitors are the mainstay drugs for its treatment. In order to discover new sources of potent AChE inhibitors, a combined strategy is presented based on AChE-inhibitory activity and chemical profiles by GC/MS, together with in silico studies. The combined strategy was applied on alkaloid extracts of five Amaryllidaceae species that grow in Colombia. Fifty-seven alkaloids were detected using GC/MS, and 21 of them were identified by comparing their mass-spectral fragmentation patterns with standard reference spectra in commercial and private library databases. The alkaloid extracts of Zephyranthes carinata exhibited a high level of inhibitory activity (IC50 = 5.97 ± 0.24 μg/mL). Molecular modeling, which was performed using the structures of some of the alkaloids present in this extract and the three-dimensional crystal structures of AChE derived from Torpedo californica, disclosed their binding configuration in the active site of this AChE. The results suggested that the alkaloids 3-epimacronine and lycoramine might be of interest for AChE inhibition. Although the galanthamine group is known for its potential utility in treating AD, the tazettine-type alkaloids should be evaluated to find more selective compounds of potential benefit for AD.
authors.affiliation: Grupo de Investigación en Sustancias Bioactivas, Facultad de Química Farmacéutica, Universidad de Antioquia UdeA, Calle 70 No. 52-21, Medellín, Colombia.
authors.forename: Natalie
authors.initials: N
authors.lastname: Cortes
authors.affiliation: Grupo de Investigación en Sustancias Bioactivas, Facultad de Química Farmacéutica, Universidad de Antioquia UdeA, Calle 70 No. 52-21, Medellín, Colombia.
authors.forename: Rafael
authors.initials: R
authors.lastname: Alvarez
authors.affiliation: Departamento de Ciencias Básicas, Fundación Universitaria Luis Amigó, SISCO, Transversal 51A No. 67B-90, Medellín, Colombia.
authors.forename: Edison H
authors.initials: EH
authors.lastname: Osorio
authors.affiliation: Grupo de Estudios Botánicos, Facultad de Ciencias Exactas y Naturales, Universidad de Antioquia UdeA, Calle 70 No. 52-21, Medellín, Colombia.
authors.forename: Fernando
authors.initials: F
authors.lastname: Alzate
authors.affiliation: Institute of Biodiversity and Ecosystem Research, 23 Acad. G. Bonchev Str., 1113 Sofia, Bulgaria.
authors.forename: Strahil
authors.initials: S
authors.lastname: Berkov
authors.affiliation: Grupo de Investigación en Sustancias Bioactivas, Facultad de Química Farmacéutica, Universidad de Antioquia UdeA, Calle 70 No. 52-21, Medellín, Colombia. Electronic address: edison.osorio@udea.edu.co.
authors.forename: Edison
authors.initials: E
authors.lastname: Osorio
mesh_terms: D000470:Alkaloids / Q000032:analysis* / Q000737:chemistry / Q000494:pharmacology; D000544:Alzheimer Disease / Q000188:drug therapy; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D006801:Humans; D019668:Liliaceae / Q000378:metabolism*; D008958:Models, Molecular; D010936:Plant Extracts / Q000494:pharmacology*
chemical_list: D000470:Alkaloids; D002800:Cholinesterase Inhibitors; D010936:Plant Extracts
keywords: Acetylcholinesterase inhibitors; Alzheimer disease; Amaryllidaceae; Amaryllidaceae alkaloids; Docking