Synthesis of Monomeric Derivatives To Probe Memoquin's Bivalent Interactions
Synthesis of Monomeric Derivatives To Probe Memoquin's Bivalent Interactions
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DOI：
10.1021/jm200691d
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发表时间：
2011-12-22
影响因子：
7.3
通讯作者：
Melchiorre, Carlo
中科院分区：
文献类型：
--
作者：
Bolognesi, Maria Laura;Chiriano, GianPaolo;Melchiorre, Carlo
制备了与多靶点先导候选物memoquin相关的八种单体同系物，并在多个靶点进行了评价，以确定其对阿尔茨海默病的影响。2-4以相似的低纳摩尔亲和力与AChE结合，并作为淀粉样蛋白聚集的有效抑制剂发挥作用。最有效的单价配体2也抑制体外BACE-1和原代鸡端脑神经元中的APP代谢。
Eight monomeric congeners, related to the multitarget lead candidate memoquin, were prepared and evaluated at multiple targets to determine their profile against Alzheimer's disease. 2-4 bind to AChE with similar low nanomolar affinities and function as effective inhibitors of amyloid aggregation. The most potent monovalent ligand 2 also inhibits BACE-1 in vitro and APP metabolism in primary chicken telencephalic neurons.