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

Background: Alzheimer's disease is a medical condition with detrimental brain health. It is majorly diagnosed in aging individuals plaque in beta) characterized by accumulated Amyloidal beta (A 1 RACE) 1 secretase APP cleavage enzyme beta neurological 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 mu M and thus was found to be the most promising lead molecule as BACE-1 inhibitor.