3-4-di-o-caffeoylquinic-acid and nemorosone

Alzheimer's disease (AD) is one of the neurodegenerative diseases, manifesting dementia, spatial disorientation, language, cognitive, and functional impairment, mainly affects the elderly population with a growing concern about the financial burden on society. Repurposing can improve the traditional progress of drug design applications and could speed up the identification of innovative remedies for AD. The pursuit of potent anti-BACE-1 drugs for AD treatment has become a pot boiler topic in the recent past and to instigate the design of novel improved inhibitors from the bee products. Drug-likeness characteristics (ADMET: absorption, distribution, metabolism, excretion, and toxicity), docking (AutoDock Vina), simulation (GROMACS), and free energy interaction (MM-PBSA, molecular mechanics Poisson-Boltzmann surface area) analyses were performed to identify the lead candidates from the bee products (500 bioactives from the honey, royal jelly, propolis, bee bread, bee wax, and bee venom) for Alzheimer's disease as novel inhibitors of BACE-1 (beta-site amyloid precursor protein cleaving enzyme (1) receptor using appropriate bioinformatics tools. Forty-four bioactive lead compounds were screened from the bee products through high throughput virtual screening on the basis of their pharmacokinetic and pharmacodynamics characteristics, showing favorable intestinal and oral absorption, bioavailability, blood brain barrier penetration, less skin permeability, and no inhibition of cytochrome P450 inhibitors. The docking score of the forty-four ligand molecules was found to be between -4 and -10.3 kcal/mol, respectively, exhibiting strong binding affinity to BACE1 receptor. The highest binding affinity was observed in the rutin (-10.3 kcal/mol), 3,4-dicaffeoylquinic acid (-9.5 kcal/mol), nemorosone (-9.5 kcal/mol), and luteolin (-8.9 kcal/mol). Furthermore, these compounds demonstrated high total binding energy -73.20 to -105.85 kJ/mol), and low root mean square deviation (0.194-0.202 nm), root mean square fluctuation (0.0985-0.1136 nm), radius of gyration (2.12 nm), number of H-bonds (0.778-5.436), and eigenvector values (2.39-3.54 nm

Topics: Aged; Alzheimer Disease; Amyloid Precursor Protein Secretases; Animals; Aspartic Acid Endopeptidases; Bees; Drug Repositioning; Humans; Ligands; Luteolin; Molecular Docking Simulation