Pharmacophore mapping-based virtual screening followed by molecular docking studies in search of potential acetylcholinesterase inhibitors as anti-Alzheimer's agents

Pravin Ambure; Supratik Kar; Kunal Roy

doi:10.1016/j.biosystems.2013.12.002

Pharmacophore mapping-based virtual screening followed by molecular docking studies in search of potential acetylcholinesterase inhibitors as anti-Alzheimer's agents

Biosystems. 2014 Feb:116:10-20. doi: 10.1016/j.biosystems.2013.12.002. Epub 2013 Dec 8.

Authors

Pravin Ambure¹, Supratik Kar¹, Kunal Roy²

Affiliations

¹ Drug Theoretics and Cheminformatics Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, India.
² Drug Theoretics and Cheminformatics Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, India. Electronic address: kunalroy_in@yahoo.com.

PMID: 24325852
DOI: 10.1016/j.biosystems.2013.12.002

Abstract

Alzheimer's disease (AD) is turning out to be one of the lethal diseases in older people. Acetylcholinesterase (AChE) is a crucial target in designing of drugs against AD. The present in silico study was carried out to explore natural compounds as potential AChE inhibitors. Virtual screening, via drug-like ADMET filter, best pharmacophore model and molecular docking analyses, has been utilized to identify putative novel AChE inhibitors. The InterBioScreen's Natural Compound (NC) database was first filtered by applying drug-like ADMET properties and then with the pharmacophore-based virtual screening followed by molecular docking analyses. Based on docking score, interaction patterns and calculated activity, the final hits were selected and these consist of coumarin and non-coumarin classes of compounds. Few hits were found to have been already reported for their AChE inhibitory activity in different literatures confirming reliability of our pharmacophore model. The remaining hits are suggested to be potential AChE inhibitors for AD.

Keywords: Acetylcholinesterase inhibitor; Alzheimer's disease; Molecular docking; Pharmacophore mapping; QSAR; Virtual screening.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acetylcholinesterase / drug effects*
Alzheimer Disease / drug therapy*
Cholinesterase Inhibitors / chemistry*
Cholinesterase Inhibitors / pharmacology
Cholinesterase Inhibitors / therapeutic use
Molecular Docking Simulation*
Quantitative Structure-Activity Relationship

Substances

Cholinesterase Inhibitors
Acetylcholinesterase