5-N-甲基苯并呋喃［3,2-b］喹啉衍生物的合成及其作为DNA嵌插剂的光谱学研究

Synthesis of 5-N-methyl-benzofuroquinoline Derivatives and Spectroscopic Studies on These Derivatives as DNA Intercalators

以生物碱白叶藤碱为出发点,依据生物电子等排体原则,设计了5-N-甲基苯并呋喃[3,2-b]喹啉母体,并参考安吖啶结构特征,合成了一系列5-N-甲基苯并呋喃喹啉的11-位苯胺衍生物,通过波谱手段确认其结构。运用紫外-可见光谱法和分子对接测定了衍生物与DNA的结合常数K和对接分数。紫外光谱实验中,衍生物与小牛胸腺DNA结合后吸收峰出现减色效应和红移现象;离子强度实验排除了表面结合模式的可能性;结合EB置换实验和分子模拟的结果,可初步推断作用模式为嵌插作用。

Based on the isostere theory and the structure of alkaloid crytolepine,5-N-methylbenzofuro［3,2-b］quinoline scaffold was designed.Referencing to the derivatization strategy of amsacrine,a series of aniline-substituted 5-N-methylbenzofuro［3,2-b］quinoline derivatives were designed and synthesized,and their structures were characterized by MS and 1H NMR spectra.The binding constants and docking sores of these derivatives with double-stranded DNA were studied by UV-Vis absorption spectra and Surflex-Dock.Surface binding mode was eliminated by ionic strength influence assay.Combined with the results from EB displacement experiments,it was proposed that these derivatives interacted with duplex DNA via intercalation binding mode.