title: Virtual screening of acetylcholinesterase inhibitors using the Lipinski's rule of five and ZINC databank.
abstract: Alzheimer's disease (AD) is a progressive and neurodegenerative pathology that can affect people over 65 years of age. It causes several complications, such as behavioral changes, language deficits, depression, and memory impairments. One of the methods used to treat AD is the increase of acetylcholine (ACh) in the brain by using acetylcholinesterase inhibitors (AChEIs). In this study, we used the ZINC databank and the Lipinski's rule of five to perform a virtual screening and a molecular docking (using Auto Dock Vina 1.1.1) aiming to select possible compounds that have quaternary ammonium atom able to inhibit acetylcholinesterase (AChE) activity. The molecules were obtained by screening and further in vitro assays were performed to analyze the most potent inhibitors through the IC50 value and also to describe the interaction models between inhibitors and enzyme by molecular docking. The results showed that compound D inhibited AChE activity from different vertebrate sources and butyrylcholinesterase (BChE) from Equus ferus (EfBChE), with IC50 ranging from 1.69 ± 0.46 to 5.64 ± 2.47 µM. Compound D interacted with the peripheral anionic subsite in both enzymes, blocking substrate entrance to the active site. In contrast, compound C had higher specificity as inhibitor of EfBChE. In conclusion, the screening was effective in finding inhibitors of AChE and BuChE from different organisms.
authors: Departamento de Bioquímica e Biologia Molecular, Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, 97105-900 Santa Maria, RS, Brazil.
authors: Pablo Andrei
authors: PA
authors: Nogara
authors: Grupo de Estudos em Bioquímica, Farmacologia e Toxicologia Molecular, Unidade Acadêmica de Serra Talhada, Universidade Federal Rural de Pernambuco, 56900-000 Serra Talhada, PE, Brazil.
authors: Rogério de Aquino
authors: Rde A
authors: Saraiva
authors: Departamento de Bioquímica e Biologia Molecular, Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, 97105-900 Santa Maria, RS, Brazil.
authors: Diones
authors: D
authors: Caeran Bueno
authors: Departamento de Bioquímica e Biologia Molecular, Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, 97105-900 Santa Maria, RS, Brazil.
authors: Lílian Juliana
authors: LJ
authors: Lissner
authors: Departamento de Bioquímica e Biologia Molecular, Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, 97105-900 Santa Maria, RS, Brazil.
authors: Cristiane
authors: C
authors: Lenz Dalla Corte
authors: Departamento de Bioquímica e Biologia Molecular, Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, 97105-900 Santa Maria, RS, Brazil.
authors: Marcos M
authors: MM
authors: Braga
authors: Departamento de Bioquímica e Biologia Molecular, Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, 97105-900 Santa Maria, RS, Brazil.
authors: Denis Broock
authors: DB
authors: Rosemberg
authors: Departamento de Bioquímica e Biologia Molecular, Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, 97105-900 Santa Maria, RS, Brazil.
authors: João Batista Teixeira
authors: JB
authors: Rocha
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000110:Acetylcholinesterase / Q000737:chemistry* / Q000378:metabolism*; D000544:Alzheimer Disease / Q000188:drug therapy / Q000201:enzymology; D000818:Animals; D002091:Butyrylcholinesterase / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D030562:Databases, Protein; D018397:Equidae / Q000378:metabolism; D006801:Humans; D062105:Molecular Docking Simulation
chemical_list: D002800:Cholinesterase Inhibitors; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase; D000109:Acetylcholine