期刊
FUTURE MEDICINAL CHEMISTRY
卷 8, 期 17, 页码 2113-2142出版社
FUTURE SCI LTD
DOI: 10.4155/fmc-2016-0103
关键词
acetylcholinesterase inhibitors; Alzheimer's disease; amyloid-beta antiaggregation; antineurodegenerative agents; antioxidants; hybrid drugs; MAO inhibitors; metal chelators; multitarget drugs; repositioning drugs
资金
- Portuguese Fundacao para a Ciencia e Tecnologia (FCT) [UID/QUI/00100/2013]
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-a-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.
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