Proposal of therapeutic curcumin derivatives for Alzheimer’s disease based on ab initio molecular simulations

Abstract Aggregation of amyloid-β peptides (Aβs) in a brain is deeply involved in the onset of Alzheimer’s disease, and various agents inhibiting the aggregation have been developed based on natural substances to suppress the onset. We here proposed novel curcumin derivatives as potent inhibitors against the aggregation and investigated their binding properties to Aβ, using protein-ligand docking and ab initio fragment molecular orbital methods. The results reveal that a curcumin derivative, in which COH3 group of the aromatic ring is replaced by OH, binds strongly to Aβ and can be a potent inhibitor against the Aβ aggregation.