Pharmacophore Modeling and Docking Studies to Investigate Potential Leads for the Development of β -Secretase APP Cleavage Enzyme-1 (BACE-1) Inhibitors
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Published:2019-06-27
Issue:7
Volume:16
Page:775-784
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ISSN:1570-1808
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Container-title:Letters in Drug Design & Discovery
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language:en
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Short-container-title:LDDD
Author:
Arya Richa1, Gupta Satya Prakash2, Paliwal Sarvesh1, Sharma Swapnil1, Madan Kirtika1, Chauhan Monika1
Affiliation:
1. Banasthali University, 304022, Banasthali, (Raj.), India 2. Department of Pharmaceutical Technology, Meerut Institute of Engineering and Technology, 250005, Meerut, India
Abstract
Background:
Alzheimer’s disease is a medical condition with detrimental brain health. It is
majorly diagnosed in aging individuals plaque in β) characterized by accumulated Amyloidal beta (A
1 BACE) 1 secretase APP cleavage enzyme βneurological areas. The ) is the target of choice that can
be exploited to find drugs against Alzheimer’s disease.
Methods:
A series of BACE-1 inhibitors with reported binding constant were considered for the development
of a feature based pharmacophore model.
Results:
The good correlation coefficient (r=0.91) and RMSD of 0.93 was observed with 30 compounds
in training set. The model was validated internally (r2test=0.76) as well as externally by Fischer validation.
The pharmacophore based virtual screening retrieved compounds that were docked and biologically
evaluated.
Conclusion:
The three structurally diverse molecules were tested by in-vitro method. The pyridine
derivative with highest fit value (6.9) exhibited IC50 value of 2.70 µM and thus was found to be the most
promising lead molecule as BACE-1 inhibitor.
Publisher
Bentham Science Publishers Ltd.
Subject
Drug Discovery,Pharmaceutical Science,Molecular Medicine
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