Department of Chemical Sciences, University of Naples Federico II, Via Cintia, I-80126, Naples, Italy.
Department of Chemical, Materials and Production Engineering, University of Naples Federico II, Piazzale V. Tecchio 80, I-80125, Naples, Italy.
Eur J Med Chem. 2022 Nov 5;241:114618. doi: 10.1016/j.ejmech.2022.114618. Epub 2022 Jul 19.
Herein we report the synthesis, conformational analysis and the evaluation of the antiviral activity of six-membered nucleoside analogues having a piperidine ring as the preorganized (deoxy)ribose bioisostere. Mutagenic nucleobase-containing nucleosides 1 and 2 were obtained by appropriate manipulation of the well-known glycomimetic agent deoxynojirimycin as easily accessible starting material. In vitro assays revealed activity of 5-iododeoxyuridine analogue 1 against all DNA viruses tested. As suggested by DFT analysis and pH-dependent NMR experiments, antiviral activity was correlated to the biomimetic character of the piperidine ring, as it is able to resemble the deoxyribose conformations adopted by natural nucleosides when interacting with viral enzymes.
在此，我们报告了具有哌啶环作为预组织（脱氧）核糖生物等排体的六元核苷类似物的合成、构象分析和抗病毒活性评估。通过对众所周知的糖模拟物去氧野尻霉素进行适当操作，获得了含有诱变碱基的核苷 1 和 2，它们是易于获得的起始材料。体外测定显示，5-碘脱氧尿苷类似物 1 对所有测试的 DNA 病毒均具有活性。正如 DFT 分析和 pH 依赖的 NMR 实验所表明的那样，抗病毒活性与哌啶环的仿生特性相关，因为它能够在与病毒酶相互作用时类似于天然核苷所采用的脱氧核糖构象。
