Computational Insights Into Marine Red Algae‐Derived Bromophenols as Dual‐Action Antioxidants and Cholinesterase Inhibitors Targeting ROS in Alzheimer's Disease

ABSTRACT

Marine red algae‐derived bromophenols are promising multifunctional candidates for Alzheimer's disease (AD) owing to their antioxidant and neuroprotective potential. In this work, an integrated computational approach was employed to evaluate their radical‐scavenging activity, Alzheimer's‐related targets, drug‐likeness, and binding stability. DFT analysis identified C4 [3‐(2,3‐dibromo‐4,5‐dihydroxyphenyl)‐2‐phenylpropanoic acid] as the most favorable antioxidant, particularly toward ROO ^• , with an interaction energy of −6.89 kcal/mol. The SET‐PT pathway was the most favorable mechanism, supported by its lower ionization potential (542.76 kcal/mol) and favorable proton dissociation energy (612.54 kcal/mol). NBO, NCI‐RDG, ELF, and QTAIM analyses further supported the stability of the C4–ROO ^• complex. Network pharmacology identified AChE and BuChE as key Alzheimer's‐related targets, while molecular docking showed favorable C4 binding affinities of −9.5 to −8.3 kcal/mol. ADMET profiling indicated favorable drug‐likeness and pharmacokinetic characteristics with comparatively low toxicity. MD and MM‐GBSA analyses further supported stable C4–AChE binding, with a predicted Δ G _bind of −40.32 kcal/mol. Overall, C4 emerges as a promising multifunctional bromophenol with antioxidant and cholinesterase‐targeting potential for AD, warranting experimental validation.