摘要
目的研究2种喹啉有机锗倍半氧化物与小牛胸腺DNA（CT － DNA）和2种人工合成的寡聚核苷酸（22聚AT碱基对d（AT）22和22聚GC碱基对d（GC）22的相互作用，以便揭示化合物的抗癌作用机制。方法综合应用紫外－可见分光光度法（UV-Vis）、热变性（melting temperature studies）、荧光光谱变化（fluorescence tition experiments）、黏度测定（viscosity measurements）等方法，研究了2种喹啉有机锗倍半氧化物与3种DNA的相互作用。结果有机锗化合物与CT-DNA结合后，它们的UV － Vis光谱均发生了不同程度的减色效应和红移现象，相对荧光强度显著增强;化合物能使DNA的热变温度（Tm）提高、黏度增强;通过荧光滴定数据计算得到相应的结合常数（10^4-10^5L/mol）。结论喹啉有机锗倍半氧化物能够与DNA以插入方式结合，喹啉基团与有机锗的协同作用增强了抗癌活性，DNA可能是其作用靶点。这些结果对进一步合成高效低毒的有机锗抗癌药物、揭示它们的抗癌作用机制具有重要的参考价值。
Objective To study the interaction of two novel qttinoline-organogermanium sesquioxides with calf thymus DNA（CT-DNA） and two synthetic oligonucleotides, d （AT） 22 and d （GC） 22, and reveal the anti- cancer mechanism of the organogermanium compounds. Methods The interaction was investigated by absorption spectroscopy, DNA thermal denaturalization, viscosity, and fluorometric titration method. The binding constants were calculated from fluorescence-titration data by nonlinear least-squares analysis. Results The new compounds could interact with DNA by intercalation. The binding constants of the compounds with CT-DNA and the synthetic oligonucleotides were found to be on the order of 104-105 L/mol. Conclusion DNA may be the primary effect target of the quinoline-organogermanium sesquioxides. These results provided the important information for the design and synthesis of new types of organogermanium compounds with stronger anticancer activity.
出处
《济宁医学院学报》
2016年第3期165-169,173,共6页
Journal of Jining Medical University
基金
Supported by the Natural Science Foundation of Shandong Province,China(ZR2011HL003)
