摘要
阿尔茨海默病(AD)是一种复杂而渐进性的神经系统退行性疾病。有效的治疗局限于对症治疗,且效果依然不太令人满意。鉴于AD的普遍和发病率的增长,有效治疗方法的开发对于公共健康至关重要。由于这种疾病病因的多因素,在寻找治疗AD的新药过程中多靶向配体(MTDL)方案是一种有前景的方法。本综述对近三年发表的多功能潜在抗AD剂的发展信息进行了更新。近期报道的大多数结构为乙酰胆碱酶抑制剂,经常被赋予一些其它性能。这些特性丰富了化合物的药理性质,不仅给该疾病的对症治疗带来希望,同时病因疗法也给予希望。在这些有益作用中,经常被报道的为抗β淀粉样聚集的活性、β分泌酶和单胺氧化酶的抑制、一种抗氧化剂和金属螯合物活性、NO释放能力及大麻素、NMDA 和组胺H3受体的相互作用。大多数的新颖分子具有异质二聚体结构,能够通过结合不同的药效团、天然产物及其衍生物或现有疗法(他克林、多奈哌齐、加兰他敏、美金刚)与多靶点相互作用。在描述的化合物中,一些可能成为AD新效疗法中的有望药物候选代表,其他的也许可以作为一种有价值的灵感。
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
Current Medicinal Chemistry
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.
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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
DOI https://dx.doi.org/10.2174/0929867321666141106122628 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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