环丙沙星衍生物的合成及其声动力活性研究

Synthesis and sonodynamic activity evaluation of ciprofloxacin derivatives

目的设计、合成系列环丙沙星衍生物,并考察其声动力活性。方法采用混合酸酐法制备了3种环丙沙星衍生物,以衍生物联合超声照射对牛血清白蛋白(BSA)的损伤程度为考核指标,借助UV-Vis光谱和荧光光谱分别研究衍生物声动力活性。同时,考察照射时间和衍生物浓度对BSA分子损伤的影响。进一步采用氧化-萃取分光光度法对衍生物的作用机制进行探究。结果在一定条件下,随着照射时间延长和衍生物浓度增加,BSA的UV-Vis光谱出现明显的增色效应,而荧光光谱则展示出越来越明显的猝灭现象。机制研究表明,环丙沙星衍生物C3声动力活性与其被超声激活后产生的活性氧有关,且以1O2和·OH为主。结论与环丙沙星及另外2种衍生物相比,衍生物C3展示出较好的声动力活性,对于高活性声敏剂的开发是一种有意义的探索。

Objective To design and synthesize ciprofloxacin derivatives,and test their sonodynamic activities.Methods Three novel ciprofloxacin derivatives were prepared by mixed anhydride method. The damage of bovine serum albumin(BSA)by the ultrasonic irradiation at the presence of synthetic derivatives was used as a index for the evaluation of sonodynamic activity of the derivatives,and the activity was assayed by the UV-Vis spectroscopy and fluorescence spectroscopy. Meanwhile,the influencing factors on the damage of BSA molecules,such as ultrasonic irradiation time and derivative concentration,were also investigated. Then,the possible mechanism of sonodynamic effect was investigated by the oxidation-extraction spectrophotometry. Results Under the certain conditions,the damage of BSA molecules was enhanced with the increases in the ultrasonic irradiation time and derivative concentration,under which the UV-Vis spectra exhibited obvious hyperchromic effect and the fluorescence spectra showed a strong fluorescence destruction owing to the synergistic effect between derivatives and ultrasound. Further investigation on the mechanism indicated that the sonodynamic effect of derivative C3 was likely related to the reactive oxygen species produced by the derivative C3 by ultrasonic irradiation,mainly1 O2 and ·OH. Conclusion Compared with ciprofloxacin and two other derivatives,the derivative C3 showed more excellent sonodynamic activity. The present result provides a reference for further investigation on the ciprofloxacin-derived new sonosensitizers.