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 

机构地区：[1]Shanghai Institute of Applied Physics,Chinese Academy of Sciences,Shanghai 201800,China [2]University of Chinese Academy of Science,Beijing 100049,China

出　　处：《Nuclear Science and Techniques》2020年第7期34-45,共12页核技术（英文）

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

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 methods.The 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 methods.In addition,95%of the solar UV irradiation that reaches the earth’s surface has wavelength[315 nm.Therefore,reducing the most effective excitation wavelength by optimizing the substituent at the1-position may be a promising strategy to alleviate the phototoxicity of FQ antibiotics.These 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 effectiveness.Delafloxacin,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 date.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 antibiotics.These findings will be beneficial to the development of novel FQ antibiotics without phototoxicity.

关 键 词：SUBSTITUENT TRANSIENT PHOTOCHEMISTRY 

分 类 号：R978.1[医药卫生—药品] TQ465[医药卫生—药学]