A review on flavonoid-based scaffolds as multi-target-directed ligands (MTDLs) for Alzheimer's disease

Alzheimer's disease (AD), the most common form of dementia, is a multifactorial neurodegenerative disease. The target enzymes inhibition including cholinesterase, beta-secretase, monoamine oxidase and inhibition of amyloid-beta aggregation as well as oxidative stress and metal chelation play an important role in the pathogenesis of AD. Chroman-4-one scaffold with benzo-gamma-pyrone network is a privileged structure in organic synthesis and drug design. A large number of research has been carried out on modified naturally occurring chromanone scaffolds and/or synthesized new analogues, to obtain effective drugs for AD management. The present review summarizes aspects related to the multi-target directed ligands (MTDLs) strategy in enzyme targets modulation performed with natural and synthesized chroman-4-one-based structures to look at their potential in the management of multifactorial Alzheimer's disease. (C) 2018 Elsevier Masson SAS. All rights reserved.