Biomedical Research Centre, University Hospital Hradec Kralove, Sokolska 581, 500 05 Hradec Kralove, Czech Republic; National Institute of Mental Health, Topolova 748, 250 67 Klecany, Czech Republic.
Biomedical Research Centre, University Hospital Hradec Kralove, Sokolska 581, 500 05 Hradec Kralove, Czech Republic; Department of Toxicology and Military Pharmacy, Faculty of Military Health Sciences, Trebesska 1575, 500 01 Hradec Kralove, Czech Republic.
Bioorg Med Chem Lett. 2021 Jul 1;43:128100. doi: 10.1016/j.bmcl.2021.128100. Epub 2021 May 10.
The search for novel and effective therapeutics for Alzheimer's disease (AD) is the main quest that remains to be resolved. The goal is to find a disease-modifying agent able to confront the multifactorial nature of the disease positively. Herewith, a family of huprineY-tryptophan heterodimers was prepared, resulting in inhibition of cholinesterase and neuronal nitric oxide synthase enzymes, with effect against amyloid-beta (Aβ) and potential ability to cross the blood-brain barrier. Their cholinesterase pattern of behavior was inspected using kinetic analysis in tandem with docking studies. These heterodimers exhibited a promising pharmacological profile with strong implication in AD.
寻找治疗阿尔茨海默病（AD）的新型有效疗法是目前尚未解决的主要问题。目标是找到一种能够积极应对疾病多因素性质的疾病修饰剂。在此，制备了一组 huprineY-色氨酸杂二聚体，其可抑制胆碱酯酶和神经元型一氧化氮合酶，对淀粉样蛋白-β（Aβ）有作用，并有潜在的穿过血脑屏障的能力。使用动力学分析与对接研究相结合，检查了它们的胆碱酯酶行为模式。这些杂二聚体表现出有希望的药理学特征，对 AD 有很强的影响。
