Memoquin: A Multi-Target-Directed Ligand as an Innovative Therapeutic Opportunity for Alzheimer's Disease

被引:109
作者
Bolognesi, Maria Laura [1 ]
Cavalli, Andrea [1 ,2 ]
Melchiorre, Carlo [1 ]
机构
[1] Univ Bologna, Alma Mater Studiorum, Dept Pharmaceut Sci, I-40126 Bologna, Italy
[2] Italian Inst Technol, Dept Drug Discovery & Dev, I-16163 Genoa, Italy
关键词
Multifunctional compounds; AD11; mice; acetylcholinesterase; amyloid; antioxidant; benzoquinones; tau hyperphosphorylation; SITE ACETYLCHOLINESTERASE INHIBITORS; NAD(P)H-QUINONE OXIDOREDUCTASE ACTIVITY; BETA-AMYLOID AGGREGATION; QUINONE REDUCTASE; OXIDATIVE STRESS; PERIPHERAL SITE; NEUROTOXICITY; DISCOVERY; MULTIFACTORIAL; PATHOGENESIS;
D O I
10.1016/j.nurt.2008.10.042
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Alzheimer's disease is currently thought to be a complex, multifactorial syndrome, unlikely to arise from a single causal factor; instead, a number of related biological alterations are thought to contribute to its pathogenesis. This may explain why the currently available drugs, developed according to the classic drug discovery paradigm of "one-molecule-one-target," have turned out to be palliative. In light of this, drug combinations that can act at different levels of the neurotoxic cascade offer new avenues toward curing Alzheimer's and other neurodegenerative diseases. In parallel, a new strategy is emerging-that of developing a single chemical entity able to modulate multiple targets simultaneously. This has led to a new paradigm in medicinal chemistry, the "multitarget-directed ligand" design strategy, which has already been successfully exploited at both academic and industrial levels. As a case study, we report here on memoquin, a new molecule developed following this strategy. The in vitro and in vivo biological profile of memoquin demonstrates the suitability of the new strategy for obtaining innovative drug candidates for the treatment of neurodegenerative diseases.
引用
收藏
页码:152 / 162
页数:11
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