BACE1 Inhibition Utilizing Organic Compounds Holds Promise as a Potential Treatment for Alzheimer’s and Parkinson’s Diseases

Authors:
Open Access
Publisher website
Google Scholar
Abstract
Background. Neurological disorders like Alzheimers disease (AD) and Parkinsons disease (PD) manifest through gradually deteriorating cognitive functions. An encouraging strategy for addressing these disorders involves the inhibition of precursor-cleaving enzyme 1 (BACE1). Objectives. In the current research, a virtual screening technique was employed to identify potential BACE1 inhibitors among selected herbal isolates. Methods. This study evaluated 79 flavonoids, anthraquinones (AQs), and cinnamic acid derivatives for their potential bloodbrain barrier (BBB) permeability. Using the AutoDock 4.0 tool, molecular docking analysis was conducted to determine the binding affinity of BBB permeable compounds to the BACE1 active site. Molecular dynamics (MD) simulations were performed to assess the stability of the docked poses of the most potent inhibitors. The interactions between the most effective plant-based inhibitors and the residues within the BACE1 catalytic site were examined before and after MD simulations. Results. Ponciretin, danthron, chrysophanol, and N-p-coumaroyltyramine were among the highest-ranking BACE1 inhibitors, with inhibition constant values calculated in the nanomolar range. Furthermore, during 10ns simulations, the docked poses of these ligands were observed to be stable. Conclusion. The findings propose that ponciretin, danthron, chrysophanol, and N-p-coumaroyltyramine might serve as potential choices for the treatment of AD and PD, laying the groundwork for the creation of innovative BACE1 inhibitors.

This publication has 49 references indexed in Scilit: