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

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.