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Pharmacophore Modeling and Docking Studies to Investigate Potential Leads for the Development of β -Secretase APP Cleavage Enzyme-1 (BACE-1) Inhibitors

[ Vol. 16 , Issue. 7 ]


Richa Arya, Satya Prakash Gupta*, Sarvesh Paliwal, Swapnil Sharma, Kirtika Madan and Monika Chauhan   Pages 775 - 784 ( 10 )


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.


β-secretase APP cleavage enzyme-1, β-secretase, docking, fluorescence, micro plate, pharmacophore, virtual screening.


Banasthali University, 304022, Banasthali, (Raj.), Department of Pharmaceutical Technology, Meerut Institute of Engineering and Technology, 250005, Meerut, Banasthali University, 304022, Banasthali, (Raj.), Banasthali University, 304022, Banasthali, (Raj.), Banasthali University, 304022, Banasthali, (Raj.), Banasthali University, 304022, Banasthali, (Raj.)

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