Toward a Rational Design of Multitarget-Directed Antioxidants: Merging Memoquin and Lipoic Acid Molecular Frameworks
Toward a Rational Design of Multitarget-Directed Antioxidants: Merging Memoquin and Lipoic Acid Molecular Frameworks
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DOI：
10.1021/jm901123n
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发表时间：
2009-12-10
影响因子：
7.3
通讯作者：
Melchiorre, Carlo
中科院分区：
文献类型：
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作者：
Bolognesi, Maria Laura;Cavalli, Andrea;Melchiorre, Carlo
新型多靶点抗氧化剂 3-6 是通过结合两种多功能先导候选物的抗氧化特征（即苯醌片段和硫辛酰功能）而设计的。然后对它们进行评估，以确定它们对阿尔茨海默病的抵抗力。它们在线粒体和 T67 细胞系中表现出抗氧化活性，并在酶促还原后得到改善。它们还表现出对β-淀粉样蛋白聚集和乙酰胆碱酯酶的平衡抑制特性，成为神经保护剂先导化合物发现的有希望的分子。
Novel multitargeted antioxidants 3-6 were designed by combining the antioxidant features, namely, a benzoquinone fragment and a lipoyl function, of two multifunctional lead candidates. They were then evaluated to determine their profile against Alzheimer's disease. They showed antioxidant activity, improved following enzymatic reduction, in mitochondria and T67 cell line. They also displayed a balanced inhibitory profile against amyloid-beta aggregation and acetylcholinesterase, emerging as promising molecules for neuroprotectant lead discovery.