Title:Recent Development of Multifunctional Agents as Potential Drug Candidates for the Treatment of Alzheimer’s Disease
Volume: 22
Issue: 3
Author(s): Natalia Guzior, Anna Wieckowska, Dawid Panek and Barbara Malawska
Affiliation:
Keywords:
Alzheimer’s disease, antioxidants, β-amyloid anti-aggregation properties, cholinesterase inhibitors, inhibitors of β-
secretase, inhibitors of monoamine oxidase A/B, multi-target-directed ligands, neuroprotective properties.
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.
