AI-Assisted SAR and Molecular Docking of Resveratrol Analogues: A Sustainable Approach to Alzheimer’s Disease Drug Discovery

Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that remains one of the most challenging global health issues. Characterized by memory loss, cognitive decline, and neuronal death, AD involves complex pathophysiological mechanisms including amyloid-β aggregation, tau hyperphosphorylation, oxidative stress, mitochondrial dysfunction, and neuroinflammation. Despite decades of research, currently approved drugs such as donepezil, rivastigmine, and memantine only provide symptomatic relief without altering disease progression. The need for new, effective, and sustainable therapeutic agents is therefore urgent.

Resveratrol, a naturally occurring polyphenol found in grapes, berries, and peanuts, has drawn immense attention for its neuroprotective, antioxidant, and anti-amyloid properties. However, its low bioavailability, rapid metabolism, and limited blood–brain barrier (BBB) penetration restrict its therapeutic potential. To overcome these limitations, structure–activity relationship (SAR) studies and molecular docking of resveratrol analogues have emerged as a promising strategy to identify more potent and bioavailable derivatives.