欧前胡素及同分异构体与DNA的作用机理及构效关系研究

Mechanism and the structure-activity relationship of imperatorin and isoimperatorin with DNA

在模拟人体生理条件下,采用紫外光谱法、荧光光谱法、DNA热变性及黏度法研究欧前胡素及同分异构体异欧前胡素与DNA的作用机制,并探讨其构效关系.紫外光谱表明,加入DNA后,欧前胡素和异欧前胡素的紫外光谱均呈现减色效应;荧光光谱显示,随着欧前胡素或异欧前胡素浓度的增大,DNA-BR的荧光被猝灭,表明欧前胡素和异欧前胡素对BR与DNA的结合存在竞争性抑制;盐效应、DNA热变性温度、黏度法等实验进一步证明欧前胡素和异欧前胡素与DNA的作用模式均为嵌插与静电混合作用模式.研究表明,欧前胡素和异欧前胡素均与DNA发生作用,且欧前胡素与DNA作用强于异欧前胡素.

The mechanism and the structure-activity relationship of imperatorin and its isomer isoimper- atorin with DNA were studied by ultraviolet spectroscopy, fluorescence spectroscopy, salt effect,DNA denaturation temperature and DNA viscosity measurement under the simulative human physiological condition. The results of ultraviolet spectroscopy showed that in the presence of DNA, the hypo- chromisity was observed on the absorption spectra of imperatorin and isoimperatorin. The fluorescence of BR-DNA was quenched with addition of imperatorin or isoimperatorin,which indicated that a strong competition for DNA binding between imperatorin and isoimperatorin with BR existed. The results of DNA denaturation temperature test and salt effects demonstrated that the binding mode of imperatorin and isoimperatorin with DNA were the intercalation and electrostatic interaction. Both imperatorin and isoimperatorin interacted with DNA and the interaction strength of imperatorin and DNA was stronger than that of isoimperatorin.