C-5位取代基对氟喹诺酮类药物光化学性质及光敏毒性影响的探究
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- 英文论文题名：Effects of C-5 substituents on the photochemistry and phototoxicity of Fluoroquinolones
- 论文作者：赵剑锋 ; 刘艳成 ; 徐宇列 ; 王文锋
- 英文论文作者：ZHAO Jian-feng ; LIU Yan-cheng ; XU Yu-lie ; WANG Wen-feng ; Shanghai Institute of Applied Physics ; Chinese Academy of Sciences ; SUniversity of Chinese Academy of Sciences
- 年：2015
- 作者机构：中国科学院上海应用物理研究所;中国科学院大学;
- 论文关键词：安妥沙星 ; 左氧氟沙星 ; 激光光解 ; 脉冲辐解 ; 光敏毒性 ; 凝胶电泳
- 英文论文关键词：Antofloxacin ; levofloxacin ; laser flash photolysis ; pulse radiolysis ; phototoxicity ; SDSPAGE gel electrophoresis
- 会议召开时间：2015-09-21
- 会议录名称：中国核科学技术进展报告（第四卷）——中国核学会2015年学术年会论文集第8册（同位素分卷、辐射研究与应用分卷、核技术工业应用分卷、核农学分卷、核医学分卷、核情报分卷）
- 语种：中文
- 分类号：TQ465
- 学会代码：EGVD
- 会议名称：中国核学会2015年学术年会
- 会议地点：中国四川绵阳
- 主办单位：中国核学会
- 学会名称：中国核学会
- 页数：6
- 文件大小：354k
- 原文格式：O
- 会议级别：全国
摘要
氟喹诺酮类药物(Fluoroquinolones,FQs)是一类应用广泛的高效广谱抗生素,其光敏毒性近来被广泛的研究。安妥沙星(ANT)和左氧氟沙星(LEV)这两种FQs结构相似,唯一的差别是安妥沙星在C-5位是氨基而左氧氟沙星是氢原子。本文通过激光光解、脉冲辐解、凝胶电泳等瞬态和稳态方法探究两者的光化学性质和光敏毒性,考察影响光敏毒性的结构因素。本文用激光光解测定了左氧氟沙星三重激发态的瞬态吸收谱,安妥沙星的三重激发态在所选取的各实验条件下均未能检测到;用脉冲辐解测定了安妥沙星、左氧氟沙星与水合电子反应的瞬态吸收谱并估算出各自的反应速率;用凝胶电泳比较了两者对溶菌酶的光敏损伤程度。凝胶电泳实验说明左氧氟沙星有较强的光敏毒性,而安妥沙星则没有。综合上述结果,C-5位加入氨基能使FQs难以产生三重激发态,有效降低光敏毒性。因为C-5位加入氨基并不会使药效降低或抗菌谱变窄,且可以减弱光敏毒性副作用,这一发现对研发新药有较好的借鉴作用。
Fluoroquinolones(FQs) is a class of efficient and broad-spectrum antibiotics which was widely used for decades.Its phototoxicity was studied extensively recently.The photochemistry and phototoxicity of two structure related Fluoroquinolones(FQs),including antofloxacin(ANT) and levofloxacin(LEV) have been studied in aqueous solution by laser flash photolysis,pulse radiolysis and gel electrophoresis.The only difference between their structures is the substituents at C-5position.Transient absorption spectra of triplet state of FQs was obtained by laser flash photolysis;their reactions with hydrated electron were observed and transient species were assigned by pulse radiolysis,respectively.Their effects of photosensitive damage to lysozyme was compared by SDSPAGE gel electrophoresis method.Based on the experimental results,amino group inserted in C-5position was responsible for the difficulty of producing triplet state which in turn decreased its phototoxicity.
Fluoroquinolones(FQs) is a class of efficient and broad-spectrum antibiotics which was widely used for decades.Its phototoxicity was studied extensively recently.The photochemistry and phototoxicity of two structure related Fluoroquinolones(FQs),including antofloxacin(ANT) and levofloxacin(LEV) have been studied in aqueous solution by laser flash photolysis,pulse radiolysis and gel electrophoresis.The only difference between their structures is the substituents at C-5position.Transient absorption spectra of triplet state of FQs was obtained by laser flash photolysis;their reactions with hydrated electron were observed and transient species were assigned by pulse radiolysis,respectively.Their effects of photosensitive damage to lysozyme was compared by SDSPAGE gel electrophoresis method.Based on the experimental results,amino group inserted in C-5position was responsible for the difficulty of producing triplet state which in turn decreased its phototoxicity.
引文
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[2]P.Ball,Adverse drug reactions!implications for the development of fluoroquinolones,J Antimicrob Chemoth,51(2003)21-27.
[3]B.E Johnson,N.K.Gibbs,J.Ferguson,Quinolone antibiotic with potential to photosensitize skin tumorigenesis,J Photoch Photobio B,37(1997)171-173.
[4]G.Klecak,F.Urbach,H.Urwyler,Fluoroquinolone antibacterials enhance UVA-induced skin tumors,J Photoch Photobio B,37(1997)174-181.
[5]M.Makinen,P.D.Forbes,F.Stenback,Quinolone antibacterials:A new class of photochemical carcinogens,J Photoch Photobio B,37(1997)182-187.
[6]A.Albini,S.Monti,Photophysics and photochemistry of fluoroquinolones,Chem Soc Rev,32(2003)238-250.
[7]E.Fasani,M.Mella,D.Caccia,S.Tassi,M.Fagnoni,A.Albini,The photochemistry of lomefloxacin.An aromatic carbene as the key intermediate in photodecomposition,Chem Commun,(1997)1329-1330.