Donepezil-like multifunctional agents: Design, synthesis, molecular modeling and biological evaluation.

摘要: Currently available drugs against Alzheimer's disease (AD) are only able to ameliorate the symptoms resulting in a moderate improvement memory and cognitive function without any efficacy preventing inhibiting progression of pathology. In an effort obtain disease-modifying anti-Alzheimer's (DMAADs) following multifactorial nature AD, we have recently developed multifunctional compounds. We herein describe design, synthesis, molecular modeling biological evaluation new series donepezil-related compounds possessing metal chelating properties, being capable targeting different enzymatic systems related AD (cholinesterases, ChEs, monoamine oxidase A, MAO-A). Among this set analogues compound 5f showed excellent ChEs inhibition potency selective MAO-A (vs MAO-B) coupled strong complexing properties for zinc copper ions, both known be involved AD. Moreover, 5f exhibited antioxidant as found by in vitro assessment. This represents novel donepezil-hydroxyquinoline hybrid with DMAAD profile paving way development class potentially treat