Czarnecka Kamila, Szymański Paweł, Girek Małgorzata, Mikiciuk-Olasik Elżbieta, Skibiński Robert, Kabziński Jacek, Majsterek Ireneusz, Malawska Barbara, Jończyk Jakub, Bajda Marek
Department of Pharmaceutical Chemistry, Drug Analyses and Radiopharmacy, Faculty of Pharmacy, Medical University of Lodz, Muszynskiego 1, 90-151 Lodz, Poland.
Department of Pharmaceutical Chemistry, Drug Analyses and Radiopharmacy, Faculty of Pharmacy, Medical University of Lodz, Muszynskiego 1, 90-151 Lodz, Poland.
Bioorg Chem. 2017 Jun;72:315-322. doi: 10.1016/j.bioorg.2017.05.003. Epub 2017 May 5.
A novel series of 9-amino-1,2,3,4-tetrahydroacridine derivatives with 2-fluorobenzoic acid or 3-fluorobenzoic acid moiety were designed, synthesized and evaluated as inhibitors of cholinesterases and aggregation of β-amyloid. In the study target compounds were very potent inhibitors of AChE and BChE. The most promising agents had higher inhibitory potency than the reference drugs which was tacrine. Ultimately, the kinetic assay shows the most active target compound 3c against AChE. Almost all of them were more potent against BChE than AChE. Compound 3c in various concentrations was tested by aggregation experiment. Inhibition of β-amyloid aggregation was 77.32% and 80.43% at 50µM and 100µM, respectively. Therefore, compound 3c is a promising agent for the treatment of AD.
设计、合成并评估了一系列新型的带有2-氟苯甲酸或3-氟苯甲酸部分的9-氨基-1,2,3,4-四氢吖啶衍生物，作为胆碱酯酶抑制剂和β-淀粉样蛋白聚集抑制剂。在该研究中，目标化合物是乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BChE）的强效抑制剂。最有前景的药物比参考药物他克林具有更高的抑制效力。最终，动力学分析表明最具活性的目标化合物3c对AChE有作用。几乎所有化合物对BChE的抑制作用都比对AChE更强。通过聚集实验测试了不同浓度的化合物3c。在50µM和100µM时，对β-淀粉样蛋白聚集的抑制率分别为77.32%和80.43%。因此，化合物3c是一种有前景的治疗阿尔茨海默病（AD）的药物。
