异优呫吨酮及其衍生物与DNA相互作用的研究

Spectrophotometric Study on the Interaction of Isoeuxanthone and Piperidinyl Isoeuxanthone Derivative with DNA

采用紫外光谱、荧光光谱、圆二色谱以及红外差谱法研究了异优呫吨酮(1,6-二羟基吨酮)(A)及其哌啶衍生物(1-羟基-6-(2-(1-哌啶基)乙氧基)呫吨酮)(B)与小牛胸腺DNA(CT-DNA)的作用方式和作用强度。结果表明,这两种化合物的紫外吸收光谱随DNA浓度的增加表现出减色效应;化合物A和B与DNA作用的结合常数分别为1.5×104,2.8×104 L/mol;DNA-EB体系的荧光强度随着两种化合物浓度的增加发生淬灭现象,化合物A和B的淬灭常数Kq分别是1.9×104,3.7×104 L/mol;两种化合物主要以嵌入方式与CT-DNA发生作用,B与DNA的结合能力比A强;并且呫吨酮芳环的嵌入使DNA螺旋变得松散、碱基堆积增强;化合物B插入后使CT-DNA的构象变化更为明显。研究结果对抗肿瘤药物的研发有一定的指导意义。

The binding mode and affinity of isoeuxanthone （1,6-dihydroxyxanthone） （A） and it＇s piperidinyl derivative （1-Hydroxy-6-（2-（1-piperidinyl） ethoxy） xanthone） （B） with calf thymus DNA were studied using absorption spectroscopy, fluorescence spectroscopy, circular dichroism spectroscopy （CD） and fourier transform infrared （FTIR） difference spectroscopy. It was found that the two compounds showed apparent hypochromism with increasing concentrations of DNA, The binding constants Kb for A and B were found to be 1.5 × 10^4 L/mol and 2.8 × 10^4 L/mol, respectively. The fluorescent intensity of DNA-EB system was quenched upon addition of A and B. The results suggest that the compounds interacted with DNA by intercalation mode and that the binding affinity of B was higher than that of A according to the calculated binding constants and fluorescent quenching constants. Moreover, the partial unwinding of the helix and the stabilization of base pairs were reflected in the changes of CD spectra. The characteristic absorption hands of FTIR attributed to base pairs also shifted. The spectral changes of intensity and shift of the B-DNA indicated more evident conformation change on addition of B than A, which is in agreement with the result of absorption spectroscopy and fluorescence spectroscopy.