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本文报道了一类以G-四联体为靶点的新型3,6-二酰氨基吨酮衍生物的设计、合成及活性研究。分子对接显示该系列化合物均以π-π堆积和沟槽插入相结合的方式作用于人端粒G-四联体,且这一结合方式经荧光光谱与紫外光谱证实,并在荧光滴定中发现化合物10c和10d对于四联体DNA具有较强的亲和力和选择性。随后经MTT法测试了筛选的化合物对三种人癌细胞株的体外抗增殖活性,其半数抑制率达到了微摩尔级。另外,PCR stop实验表明化合物10c和10d能够有效抑制端粒酶的扩增能力。
This paper reports the design, synthesis and activity of a class of novel 3,6-diamidoxanthone derivatives targeting G-quadruplex. Molecular docking showed that these compounds all interacted with human telomere G-quadruplex by π-π stacking and groove insertion, and this binding mode was confirmed by fluorescence and UV spectra and found in fluorescence titration Compounds 10c and 10d have strong affinity and selectivity for the quadruplex DNA. Subsequently, the anti-proliferative activity of the screened compounds on three human cancer cell lines was tested by MTT assay, and the half-inhibitory rate thereof reached the micromolar level. In addition, PCR stop experiments showed that compounds 10c and 10d could effectively inhibit the ability of telomerase to amplify.