Synthesis and evaluation of donepezil–ferulic acid hybrids as multi-target-directed ligands against Alzheimer's disease

Abstract

A novel family of donepezil–ferulic acid hybrids were designed, synthesized and biologically evaluated as multi-target-directed ligands against Alzheimer's disease by fusing a fragment of donepezil and ferulic acid.

Design, synthesis and evaluation of novel cinnamic acid derivatives bearing N-benzyl pyridinium moiety as multifunctional cholinesterase inhibitors for Alzheimer’s disease

“…When FeSO 4 was added, a red shift in the maximum absorption from 216 nm to 226 nm occurred, suggesting that compound 5l coordinates with Fe 2+ . The complexation ability of compound 5l might be ascribed to the dimethoxy group on the cinnamic acid moiety and to the amide moiety of the compound 46 , 33 .…”

Donepezil: A review of the recent structural modifications and their impact on anti-Alzheimer activity

“…Molecular modeling studies of compound 52 presented cation-π interaction, π-π interactions and hydrophobic interactions with BuChE but only hydrophobic interactions were observed with AChE which may be the reason for its selectivity for BuChE (Sang et al, 2017). Xu et al (2016) combined the pharmacophores of donepezil and ferulic acid to produce new hybrid molecules. Compound 53 displayed the prominent inhibition of electric eel AChE and equine BuChE having IC 50 values of 0.398 μM and 0.976 μM respectively.…”

Structure-based design, synthesis, and evaluation of structurally rigid donepezil analogues as dual AChE and BACE-1 inhibitors

“…Identification of MTDLs centered on BACE-1 inhibition is limited owing to the complexity of obtaining a balanced inhibitory profile against multiple targets [18]. Therefore, development of hybrid lead compounds that are based on similarity to FDA approved AD therapeutics is gaining considerable attention with the aim of identification of potent MTDLs [19][20][21]. Profiling of donepezil template into BACE-1 inhibition was achieved in compound 3 (Figure 1) through introduction of a double bond to the indanone moiety.…”