Synthesis of 8-hydroxyquinoline glycoconjugates and preliminary assay of their β1,4-GalT inhibitory and anti-cancer properties
作者:Monika Krawczyk、Gabriela Pastuch-Gawolek、Anna Mrozek-Wilczkiewicz、Michal Kuczak、Magdalena Skonieczna、Robert Musiol
DOI:10.1016/j.bioorg.2018.11.047
日期:2019.3
in designing a new active agents with therapeutic potential. Its connections with the sugar unit is formed to improve the pharmacokinetic properties. The broad spectrum of activity of quinoline derivatives, especially glycoconjugates, is often associated with the ability to chelate metal ions or with the ability to intercalate into DNA. Simple and effective methods of synthesis glycoconjugates of 8-hydroxyquinoline
8-羟基喹啉支架是一种特权结构,用于设计具有治疗潜力的新型活性剂。其与糖单元的连接被形成以改善药代动力学性质。喹啉衍生物,尤其是糖缀合物的广谱活性通常与螯合金属离子的能力或与插入DNA的能力有关。已经开发了简单有效的合成8-羟基喹啉和8-羟基喹哪啶衍生物的糖缀合物的方法,所述糖缀合物在其结构中包含O-糖苷键或1,2,3-三唑接头。测试获得的糖缀合物抑制β-1,4-半乳糖基转移酶以及抑制癌细胞增殖的能力。发现使用的糖缀合策略既影响活性的提高又影响8-HQ衍生物的生物利用度的提高。它们的活性取决于附着的糖的类型,糖部分中保护基的存在以及糖和喹诺酮苷元之间的连接基的存在。