Scaffold morphing and in silico studies of potential BACE1 (β‐secretase) inhibitors: A hope for newer dawn in anti‐Alzheimer therapeutics

Abstract

AbstractBackgroundAD (Alzheimer’s disease) is the prime causes for 65‐85% cases of senile dementia occurs due to the plaques aggregation and tangles formation in various parts of brains neurons (cortical and hippocampal) leading to brain cell death. The major cause of AD is the extracellular plaques accretion made of β‐amyloid protein. The β‐secretase enzyme also known as BACE‐1 is the key player behind this phenomenon catalyzing the rate determining step of the reactions generating β‐amyloid. Therefore, efforts are being applied for research and development of novel entities that can inhibit the BACE‐1 enzyme and thus halting the plaque build‐up.MethodIn our study, we analyzed some of the analogues of Elenbecestat, which is a β‐secretase inhibitor currently in clinical trials designed by using scaffold morphing and structure‐based designing approach with a superior therapeutic profile, followed by in silico screening i.e. pharmacokinetics and docking methodologies.ResultThe designed molecules showed good interactions with the active pockets (Asp32 and Asp228, catalytic dyad residues) of β‐secretase protein and having drug likeliness properties.ConclusionHenceforward, molecular dynamic studies are required to fully establish their possible utility as the promising BACE1 inhibitors.