Virtual Screening of Acetylcholinesterase Inhibitors Using the Lipinski’s Rule of Five and ZINC Databank
Joint Authors
da Rocha, João Batista Teixeira
Caeran Bueno, Diones
Dalla Corte, Cristiane L.
Nogara, Pablo Andrei
Lissner, Lílian Juliana
Braga, Marcos M.
Rosemberg, Denis Broock
Saraiva, Rogério de Aquino
Source
Issue
Vol. 2015, Issue 2015 (31 Dec. 2015), pp.1-8, 8 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2015-01-22
Country of Publication
Egypt
No. of Pages
8
Main Subjects
Abstract EN
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.
American Psychological Association (APA)
Nogara, Pablo Andrei& Saraiva, Rogério de Aquino& Caeran Bueno, Diones& Lissner, Lílian Juliana& Dalla Corte, Cristiane L.& Braga, Marcos M.…[et al.]. 2015. Virtual Screening of Acetylcholinesterase Inhibitors Using the Lipinski’s Rule of Five and ZINC Databank. BioMed Research International،Vol. 2015, no. 2015, pp.1-8.
https://search.emarefa.net/detail/BIM-1057082
Modern Language Association (MLA)
Nogara, Pablo Andrei…[et al.]. Virtual Screening of Acetylcholinesterase Inhibitors Using the Lipinski’s Rule of Five and ZINC Databank. BioMed Research International No. 2015 (2015), pp.1-8.
https://search.emarefa.net/detail/BIM-1057082
American Medical Association (AMA)
Nogara, Pablo Andrei& Saraiva, Rogério de Aquino& Caeran Bueno, Diones& Lissner, Lílian Juliana& Dalla Corte, Cristiane L.& Braga, Marcos M.…[et al.]. Virtual Screening of Acetylcholinesterase Inhibitors Using the Lipinski’s Rule of Five and ZINC Databank. BioMed Research International. 2015. Vol. 2015, no. 2015, pp.1-8.
https://search.emarefa.net/detail/BIM-1057082
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1057082