Here we present a novel family of carbohydrate conjugates based on the 2-aryl-imidazo[4,5-f][1,10]phenanthroline core modified with carbohydrates (carb-APIPs). The hybrid compounds were prepared by direct treatment of the unprotected carbohydrate with 2-(4-aminophenyl)-1H-imidazo[4,5-f][1,10]phenanthroline (APIP). The N-glycosylation reactions with the monosaccharides tested afforded stereoselectively the more stable N-β-glycopyranosylamines that, in solution, underwent a dynamic equilibrium leading to anomeric mixtures with a small participation of the α isomer. DNA interaction experiments with telomeric G-quadruplex DNA included DNA FRET melting assays, circular dichroism, and equilibrium dialysis and revealed that the novel carb-APIPs bind the G-quadruplex structure with high affinity. Interestingly, the presence of the carbohydrate confers good selectivity towards the telomeric quadruplex structure, as suggested by competition DNA FRET melting assays. Besides the extended aromatic surface that allows π-stacking interactions, the carbohydrate part of the conjugate may contribute to groove binding recognition, as indicated by viscosity experiments. In addition, the novel carb-APIPs showed significant cytotoxic properties in PC3 and HeLa cells and, to a lesser extent, in MCF7 cells and normal human fibroblasts (HFF1).

在这里，我们提出了一个基于 2-芳基咪唑并[4,5-f][1,10] 菲咯啉核心的碳水化合物共轭物家族（carb-APIPs）。通过用 2-(4- a mino phenyl )-1 H - i midazo[4,5-f][1,10] p heanthroline (APIP)直接处理未保护的碳水化合物来制备杂化化合物。与测试的单糖的N-糖基化反应立体选择性地提供了更稳定的N-β-吡喃葡萄糖胺在溶液中经历动态平衡，导致异头混合物，α 异构体的参与很少。DNA 与端粒 G-四链体 DNA 的相互作用实验包括 DNA FRET 熔解测定、圆二色性和平衡透析，并揭示了新型 carb-APIP 以高亲和力结合 G-四链体结构。有趣的是，碳水化合物的存在赋予了对端粒四链体结构的良好选择性，正如竞争性 DNA FRET 熔解分析所表明的那样。如粘度实验所示，除了允许 π 堆叠相互作用的扩展芳香表面外，缀合物的碳水化合物部分可能有助于凹槽结合识别。此外，新型 carb-APIPs 在 PC3 和 HeLa 细胞中显示出显着的细胞毒性，并且，