Effects of N-1 substituent on the phototoxicity of fluoroquinolone antibiotics: comparison of pefloxacin and difloxacin

作     者：Jian-Feng Zhao Yan-Cheng Liu Yu-Lie Xu Wen-Feng Wang Jian-Feng Zhao;Yan-Cheng Liu;Yu-Lie Xu;Wen-Feng Wang

作者机构：Shanghai Institute of Applied PhysicsChinese Academy of SciencesShanghai 201800China University of Chinese Academy of ScienceBeijing 100049China 

出 版 物：《Nuclear Science and Techniques》 (核技术（英文）)

年 卷 期：2020年第31卷第7期

页      面：34-45页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 100705[医学-微生物与生化药学] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China(No.21173252) 

主　　题：substituent transient photochemistry 

摘      要：The photophysics and photochemistry of pefloxacin(PEF),a 1-ethyl-substituted fluoroquinolone(FQ)antibiotic,were studied using transient,steady-state experimental methods and computational *** fundamental photoproperties of PEF and its phototoxicity toward lysozyme,a single-chain protein,were compared with those of a 1-fluorophenyl-substituted FQ antibiotic,difloxacin(DIF).The results showed that the phototoxicity was significantly decreased by the insertion of the bulky1-fluorophenyl substituent(the phototoxicity of DIF was approximately one-quarter of that observed for PEF).This trend was attributed to the lowest lying singlet state with sizeable oscillator strength(f C 0.1)being shifted from319 nm in PEF to 266 nm in DIF upon the insertion of the bulky substituent at the 1-position,as investigated by using computational *** addition,95%of the solar UV irradiation that reaches the earth’s surface has wavelength[315 ***,reducing the most effective excitation wavelength by optimizing the substituent at the1-position may be a promising strategy to alleviate the phototoxicity of FQ *** findings may be applied to other FQ antibiotics because a large number of phototoxicity studies on FQ antibiotics with different substituents at the 1-position can prove these finding’s ***,an FQ antibiotic bearing a chlorine and bulky substituent at the 8-and 1-positions,respectively,exhibits no phototoxicity is the most recent example reported to *** the best of our knowledge,this is the first transient and steady-state study of the effect of the N-1 substituent on the photochemistry and phototoxicity of FQ *** findings will be beneficial to the development of novel FQ antibiotics without phototoxicity.