Cyanobacterial metabolites as novel inhibitors of BACE1 implicated in Alzheimer's disease through in silico approaches

Alzheimer's disease (AD) is a complex neurodegenerative disease with a limited number of therapeutic options. β-Secretase 1 (BACE1) is a key enzyme involved in the production of amyloid beta peptides, which are central to AD pathology. Targeting BACE1 has emerged as a promising strategy for the treatment of AD. Therefore, the present study aimed to discover novel drug candidates from cyanobacteria for the treatment of AD through in silico research. In this study, Schrödinger tools were used to study the binding affinities and interactions of cyanobacteria metabolites with BACE1. Almost 120 cyanobacteria metabolites against BACE1 were used for the computational investigation. Ultimately, four marine-derived compounds, namely lyngbyastatin 7, homodolastin 3, lyngbyabellin E1, and symplostatin analogue 4, showed strong binding affinities to the active site of BACE1, forming crucial hydrogen bonds and hydrophobic interactions. The binding energy values of these compounds suggest their potential as BACE1 inhibitors. Furthermore, molecular dynamics simulations confirmed the stability of these ligand-protein complexes over a period of 25 ​ns? Our results provide valuable insights into the potential of lyngbyastatin 7, homodolastin 3, lyngbyabellin E1, and symplostatin analog 4 as effective drugs for inhibiting BACE1. These marine-derived compounds are promising for further in vitro and in vivo studies. The present research suggests that these molecules could offer new avenues for the development of novel therapeutics for the treatment of Alzheimer's disease.