多功能剂作为治疗阿尔茨海默病的潜在药物的最新进展

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:

关键词: 阿尔茨海默病，抗氧化剂，抗β淀粉样聚集的特性，胆碱酯酶抑制剂，β分泌酶抑制剂，单胺氧化酶A/B抑制剂，多靶向配体，神经保护功能

摘要: 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.

Cite this article as:

Guzior Natalia, Wieckowska Anna, Panek Dawid and Malawska Barbara, Recent Development of Multifunctional Agents as Potential Drug Candidates for the Treatment of Alzheimer’s Disease, Current Medicinal Chemistry 2015; 22 (3) . https://dx.doi.org/10.2174/0929867321666141106122628