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.
Financial & competing interests disclosure
The authors thank the Portuguese Fundação para a Ciência e Tecnologia (FCT) for financial support with the project UID/QUI/00100/2013. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.