title: Recent progress in repositioning Alzheimer's disease drugs based on a multitarget strategy.
abstract: Alzheimer's disease (AD) is a serious progressive neurological disorder, characterized by impaired cognition and profound irreversible memory loss. The multifactorial nature of AD and the absence of a cure so far have stimulated medicinal chemists worldwide to follow multitarget drug-design strategies based on repositioning approved drugs. This review describes a summary of recently published works focused on tailoring new derivatives of US FDA-approved acetylcholinesterase inhibitors, in addition to huperzine (a drug approved in China), either by hybridization with other pharmacophore elements (to hit more AD targets), or by combination of two FDA-approved drugs. Besides the capacity for improving the cholinergic activity, these polyfunctional derivatives are also able to tackle other important neuroprotective properties, such as anti-β-amyloid aggregation, scavenging of radical oxygen species, modulation of redox-active metals or inhibition of monoamine oxidase, thereby resulting in potentially novel and more effective therapeutics for the treatment of AD.
authors: Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Av Rovisco Pais 1, 1049-001 Lisboa, Portugal.
authors: M Amélia
authors: MA
authors: Santos
authors: Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Av Rovisco Pais 1, 1049-001 Lisboa, Portugal.
authors: Karam
authors: K
authors: Chand
authors: Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Av Rovisco Pais 1, 1049-001 Lisboa, Portugal.
authors: Sílvia
authors: S
authors: Chaves
keywords: Alzheimer's disease; MAO inhibitors; acetylcholinesterase inhibitors; amyloid-β antiaggregation; antineurodegenerative agents; antioxidants; hybrid drugs; metal chelators; multitarget drugs; repositioning drugs