QSAR and Molecular Modeling Studies on a Series of Pyrrolidine Analogs Acting as BACE-1 Inhibitors

Author(s): Richa Arya, Satya Prakash Gupta*, Sarvesh Paliwal, Seema Kesar, Achal Mishra, Yenamandra Subrahmanya Prabhakar

Journal Name: Letters in Drug Design & Discovery

Volume 16 , Issue 7 , 2019

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Graphical Abstract:


Background: β-Site amyloidal precursor protein (APP) cleavage enzyme (BACE-1) is reported as prime cause for progession of Alzheimer’s disease (AD). It is a form of dementia characterized by degeneration of neurones in brain. Therefore, attempts have been made to find potent inhibitors of this enzyme.

Methods: The paper presents an division-based 2D quantitative structure-activity relationship (QSAR) study on a series of BACE-1 inhibitors to analyse the structural features that may be important to increase the potency of the compounds.

Results: The study led to predict some potential leads for the development of potent inhibitors of BACE-1. One of the molecule with pyrrolidine and pyrrolidinone substitutions exhibited drugreceptor interactions comparable with reference drug.

Conclusion: The hydrogen-bond interactions between the molecules and the receptor basically control the BACE-1 inhibition activity of the compounds.

Keywords: Beta-secretase 1 (BACE-1) inhibitors, beta-site APP cleaving enzyme 1, Quantitative structure-activity relationship (QSAR), MLR, Alzheimer's disease.

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Article Details

Year: 2019
Page: [746 - 760]
Pages: 15
DOI: 10.2174/1570180815666180627124422
Price: $65

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