In Silico Design of Multi-Target Compound Combinations against Alzheimer's Disease

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with complex pathophysiology involving multiple targets such as amyloid beta (Aβ) and tau proteins. Current single-target drugs offer limited therapeutic benefits, highlighting the urgent need for a multi-target approach. This study aims to design and evaluate multi-target compound combinations (MTCCs) using in silico methods, focusing on six natural compounds. They are curcumin, glycitein, kaempferol, squalene, astaxanthin, and β-sitosterol, selected for their neuroprotective and anti-AD potential. Using strategies including linking, fusing, and merging, we propose novel MTCCs targeting both Aβ and tau. Through molecular docking, molecular dynamics simulation, and ADME/T profiling, we assess the binding affinity, pharmacokinetics, and synergistic potential of the combinations. Our results are expected to identify optimal MTCCs with superior efficacy compared to individual compounds or FDA-approved drugs. This integrative approach may accelerate the development of next-generation multi-target therapies for AD and contribute to the field of precision neuropharmacology.