Recent development of multifunctional agents as potential drug candidates for the treatment of Alzheimer's disease.

Abstract:

:Alzheimer's disease (AD) is a complex and progressive neurodegenerative disorder. The available therapy is limited to the symptomatic treatment and its efficacy remains unsatisfactory. In view of the prevalence and expected increase in the incidence of AD, the development of an effective therapy is crucial for public health. Due to the multifactorial aetiology of this disease, the multi-target-directed ligand (MTDL) approach is a promising method in search for new drugs for AD. This review updates information on the development of multifunctional potential anti-AD agents published within the last three years. The majority of the recently reported structures are acetylcholinesterase inhibitors, often endowed with some additional properties. These properties enrich the pharmacological profile of the compounds giving hope for not only symptomatic but also causal treatment of the disease. Among these advantageous properties, the most often reported are an amyloid-β antiaggregation activity, inhibition of β-secretase and monoamine oxidase, an antioxidant and metal chelating activity, NOreleasing ability and interaction with cannabinoid, NMDA or histamine H3 receptors. The majority of novel molecules possess heterodimeric structures, able to interact with multiple targets by combining different pharmacophores, original or derived from natural products or existing therapeutics (tacrine, donepezil, galantamine, memantine). Among the described compounds, several seem to be promising drug candidates, while others may serve as a valuable inspiration in the search for new effective therapies for AD.

journal_name

Curr Med Chem

authors

Guzior N,Wieckowska A,Panek D,Malawska B

doi

10.2174/0929867321666141106122628

subject

Has Abstract

pub_date

2015-01-01 00:00:00

pages

373-404

issue

3

eissn

0929-8673

issn

1875-533X

pii

CMC-EPUB-63232

journal_volume

22

pub_type

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