双羧型1,8-萘酰亚胺探针与DNA的键合行为及抗肿瘤作用

DNA Binding and Anticancer Activity of Double Carboxyl 1,8-Naphthoylimide with Side Chains

在合成一系列具有不同亚胺基侧链长度双羧基型1,8-萘酰亚胺探针的基础上,采用红外光谱、紫外可见吸收光谱、荧光光谱、圆二色谱和差热分析试验研究探针与小牛胸腺DNA(Ct-DNA)的键合行为.同时通过四甲基偶氮唑蓝(MTT)染色法研究化合物对A549(人肺癌细胞)、Hela(人宫颈癌细胞)、Bel-7402(人肝癌细胞)和HL-60(白血病细胞)等细胞株的体外抗肿瘤活性,结果表明a～e探针作为DNA嵌入剂与Ct-DNA作用显示出中性粘合.此外,将a～e探针加入到小牛胸腺DNA(Ct-DNA)的溶液中后,荧光发射谱图中产生新的发射峰,这表明探针嵌入小牛胸腺DNA(Ct-DNA)中.因此,可以将其作为DNA嵌入剂且探针a对A549细胞显示良好的抑制活性,优于阳性对照顺铂.

A series of novel double carboxyl 1,8-naphthoylimine probes with side chains at different lengths were synthesized,and their DNA binding properties were investigated by IR,UV-Vis,fluorescence,circular dichroism(CD)spectroscopies and thermal denaturation experiment.The results showed that compounds a to e as the DNA intercalating agents exhibited binding affinities with Ct-DNA.More interestingly,enhancement of the fluorescence emission peaks was found in the complexes of a to e with Ct-DNA solu-tion,so this would make these probes as potential DNA intercalating agents.Furthermore,the anticancer activity was evaluated against different tumor cell lines(human hepatocellular carcinoma Bel-7402,cells,human promyelocytic leukemia HL-60 cells,human lung cancer A549 cell,human cervical carcinoma Hela cell).Compound a exhibited potent anticancer activity against A549 cell line with IC50,which was better than the positive control drug(cisplatin)