Bolognesi Maria Laura, Cavalli Andrea, Valgimigli Luca, Bartolini Manuela, Rosini Michela, Andrisano Vincenza, Recanatini Maurizio, Melchiorre Carlo
Department of Pharmaceutical Sciences, A. Mangini, Alma Mater Studiorum, Bologna University, Italy.
J Med Chem. 2007 Dec 27;50(26):6446-9. doi: 10.1021/jm701225u. Epub 2007 Nov 30.
A design strategy to convert a dual-binding site AChE inhibitor into triple functional compounds with promising in vitro profile against multifactorial syndromes, such as Alzheimer's disease, is proposed. The lead compound bis(7)-tacrine (2) was properly modified to confer to the new molecules the ability of chelating metals, involved in the neurodegenerative process. The multifunctional compounds show activity against human AChE, are able to inhibit the AChE-induced amyloid-beta aggregation, and chelate metals, such as iron and copper.
提出了一种设计策略，旨在将双结合位点乙酰胆碱酯酶抑制剂转化为具有三重功能的化合物，这些化合物在体外对诸如阿尔茨海默病等多因素综合征具有良好的活性。先导化合物双（7）-他克林（2）经过适当修饰，使新分子具有螯合参与神经退行性过程的金属的能力。这些多功能化合物对人乙酰胆碱酯酶具有活性，能够抑制乙酰胆碱酯酶诱导的β-淀粉样蛋白聚集，并能螯合铁和铜等金属。
