Novel 3-aminobenzofuran derivatives as multifunctional agents for the treatment of Alzheimer’s disease

Abstract

A novel multifunctional series of 3-aminobenzofuran derivatives 5a-p were designed and synthesized as potent inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The target compounds 5a-p were prepared via a three-step reaction, starting from 2-hydroxy benzonitrile. In vitro anti-cholinesterase activity exhibited that most of the compounds had potent acetyl- and butyrylcholinesterase inhibitory activity. In particular, compound 5f containing 2-fluorobenzyl moiety showed the best inhibitory activity. Furthermore, this compound showed activity on self- and AChE-induced Aβ-aggregation and MTT assay against PC12 cells. The kinetic study revealed that compound 5f showed mixed-type inhibition on AChE. Based on these results, compound 5f can be considered as a novel multifunctional structural unit against Alzheimer’s disease.

Exploiting butyrylcholinesterase inhibitors through a combined 3-D pharmacophore modeling, QSAR, molecular docking, and molecular dynamics investigation

“…in this dataset total 68 compounds for used as a BuChE inhibitors. [38][39][40][41][42] Aer starting using BioChemdraw, the inhibitors' 2-D chemical structures. Dataset were curated by using alvamolecule.…”

“…[35][36][37] The current study, the pharmacophore modelling, eld and atom-based QSAR models, and GA-MLR-based models to evaluate the QSAR of a series of 6-methoxy-1-tetralone, 3-aminobenzofuran, arylisoxazoles, quinolotacrine, and methylindolinone-1,2,3-triazole derivatives. [38][39][40][41][42] In addition, the created models are used to create new BuChE inhibitor models with enhanced bioactivity. Additionally, the developed compounds are subjected to investigations of their affinity for the BuChE enzyme, drug-like properties, and molecular dynamics to determine the stability of their complexes with the target receptor, respectively.…”

Recent Advancement of Benzofuran in Treatment of Alzheimer’s Disease

“…AChE is the most important enzyme in the catalytic breakdown of ACh [95] , as AD advances, the concentration of ACh in the brain decreases. It also binds to A, increasing A peptide aggregation [96] .…”

“…Hasanvand et al [96] reported 3-aminobenzofuran based derivatives and evaluated their potency against AChE and BuChE. Among them, compound 25 which has a 2-fluorobenzyl moiety (fig.…”