Department of Organic Chemistry, Bioorganic Chemistry and Biotechnology, Faculty of Chemistry, Silesian University of Technology, Krzywoustego 4, 44-100 Gliwice, Poland; Biotechnology Centre, Silesian University of Technology, Krzywoustego 8, 44-100 Gliwice, Poland.
Department of Organic Chemistry, Bioorganic Chemistry and Biotechnology, Faculty of Chemistry, Silesian University of Technology, Krzywoustego 4, 44-100 Gliwice, Poland; Biotechnology Centre, Silesian University of Technology, Krzywoustego 8, 44-100 Gliwice, Poland.
Bioorg Chem. 2019 Mar;84:326-338. doi: 10.1016/j.bioorg.2018.11.047. Epub 2018 Nov 24.
8-Hydroxyquinoline scaffold is a privileged structure used 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 and 8-hydroxyquinaldine derivatives, containing an O-glycosidic bond or a 1,2,3-triazole linker in their structure, have been developed. The obtained glycoconjugates were tested for their ability to inhibit β-1,4-Galactosyltransferase, as well as inhibit cancer cell proliferation. It was found that used glycoconjugation strategy influenced both improvement of activity and improvement of the bioavailability of 8-HQ derivatives. Their activity depends on type of attached sugar, presence of protecting groups in sugar moiety and presence of a linker between sugar and quinolone aglycone.
8-羟基喹啉骨架是设计具有治疗潜力的新活性药物的一种优势结构。它与糖单元的连接是为了改善药物的药代动力学性质。喹啉衍生物，特别是糖缀合物的广谱活性通常与螯合金属离子的能力或与 DNA 插入的能力有关。已经开发出了简单有效的合成方法，用于合成结构中含有 O-糖苷键或 1,2,3-三唑键的 8-羟基喹啉和 8-羟基喹哪啶衍生物的糖缀合物。对所得糖缀合物进行了抑制β-1,4-半乳糖基转移酶以及抑制癌细胞增殖的能力测试。结果发现，所使用的糖缀合策略既可以提高活性，又可以提高 8-HQ 衍生物的生物利用度。它们的活性取决于所连接的糖的类型、糖部分中保护基团的存在以及糖和喹啉苷元之间的连接键的存在。
