Graph Theoretical Network Analysis and Pharmacoinformatics-Based Investigation of Bioactive Compounds from Semecarpus anacardium Linn. for Alzheimer’s Disease

Abstract

Alzheimer’s disease is a highly prevalent disease that has affected over 50 million people worldwide. It is mainly caused by the continuous deposition of amyloid-[Formula: see text] peptide (A[Formula: see text]. Acetylcholinesterase (AChE), N-methyl D-aspartate (NMDA), Tau-Tubulin kinase 1 (TTBK1) and [Formula: see text]-secretase 1 (BACE-1) are potential targets to treat Alzheimer’s disease and to reduce the pathogenesis; amongst, BACE-1 is preferred owing to its capacity in minimizing the accumulation of A[Formula: see text]. This study explored Semecarpus anacardium Linn.-derived phytocompounds and their interaction with BACE-1. The phytochemicals of S. anacardiumLinn. were retrieved from the IMPPAT database. The factual targets (AChE, BACE-1, NMDA and TTBK1) of Alzheimer’s disease are identified by the graph theoretical network analysis, and are docked with a total of eight bioactive compounds from S. anacardium Linn. Interestingly, the docking score was significant (−12 kcal × mol[Formula: see text] for the interactions of amentoflavone with BACE-1. The co-crystallized ligand of BACE-1 (2-imino-3-methyl-5,5-diphenylimidazolidin-4-one) was considered for further studies and revealed a superior binding affinity (−8.7 kcal × mol[Formula: see text]. Molecular dynamics (MD) simulation and Density Functional Theory (DFT) analyzed the conformational stability of amentoflavone and BACE-1 complex. Furthermore, S. anacardium Linn. seemed to be nontoxic against U87-MG cells in vitro. These results from in silico prediction suggest that the derivatives of S. anacardium Linn. possess a significant interaction with the BACE-1 and provide a favorable direction to prevent aggregation of A[Formula: see text] peptides.