史玉敏 严恒 王俊 陈洪国

摘要：抗生素是治疗细菌感染的主要手段。然而，由于长时间对其不恰当使用甚至滥用，耐药菌不断涌现，导致传统抗生素的疗效不断下降。目前，治疗耐药菌感染的疗法屈指可数。因此，耐药菌已严重威胁人类生命健康，开发新型抗耐药菌药物势在必行。喹诺酮尤其是氟喹诺酮类抗生素是仅次于头孢菌素类药物的第二大类抗生素，具有抗菌谱广、抗菌活性高和毒副作用低等特点，在临床上广泛用于各种细菌感染的治疗。尽管致病菌对喹诺酮类抗生素也产生了耐药性，喹诺酮杂合体由于嵌入了其他抗菌药效团，可同时作用于不同的药物靶点，具有克服耐药性的潜力。本文将着重介绍近5年来所开发的具有抗耐药菌活性的喹诺酮杂合体的最新研究进展，为进一步合理设计此类杂合体提供一定的理论支持。

关键词：氟喹诺酮；杂合体；抗菌；耐药菌；构-效关系

中图分类号：R978.1文献标志码：A

The anti-drug-resistant bacteria activity of fluoroquinolone hybrids

Shi Yumin1，2， Yan Heng3， Wang Jun1，2， and Chen Hongguo1，2，*

（1 School of Nuclear Technology and Chemistry & Biology， Hubei University of Science and Technology， National Forestry and  Grassland Administration Engineering Research Center for Osmanthus fragrans， Xianning 437100; 2 Hubei Engineering

Research Center for Fragrant Plants， Hubei University of Science and Technology， Xianning 437100;

3 Hubei Provincial Institute for Food Supervision and Test， Wuhan 430075）

Abstract Antibiotics are the mainstay for the treatment of bacterial infections. The rapid development of drug-resistant bacteria due to the improper and overuse of antibiotics has been severely affected clinical effectiveness of current available conventional antibiotics. Due to the limitation of effective drugs， drug-resistant bacteria have already become one of the daunting global challenges， calling for novel antibiotics with anti-drug-resistant bacterial potential. Fluoroquinolones possess broad antibacterial spectrum， high activity， and low side effects. Accordingly， fluoroquinolone antibiotics are widely used in clinical treatment of various bacterial infections. Although pathogens have also developed resistance to fluoroquinolone antibiotics， fluoroquinolone hybrids embedding other antibacterial pharmacophores can act on different drug targets at the same time and have the potential to overcome drug resistance. This manuscript discusses the anti-drug-resistant bacteria activity of fluoroquinolone hybrids and summarizes the structure-activity relationship.

Key words Fluoroquinolone; Hybrid; Antibacterial; Drug-resistant bacteria; Structure-activity relationship

抗生素按照化學结构可分为喹诺酮类抗生素、β-内酰胺类抗生素、大环内酯类、四环素类、磺胺类、糖肽类和氨基糖苷类抗生素等[1-2]。自1928年发现青霉素以来，于20世纪40年代开启了抗生素研发的黄金时代，各种抗生素不断问世[3-4]。抗生素改变了现代医学，拯救了无数人的生命、使人类的平均寿命得到了显著延长[5-6]。因此，抗生素的应用被认为是20世纪最大的医学突破，尤其是1962年发现首个喹诺酮类药物萘啶酸[7-8]之后。经过60年的发展，这类药物日新月异，具有抗菌谱广、抗菌活性强、口服吸收好、组织浓度比较高和不良反应较低等诸多优点，广泛用于各种致病菌引起的尿路、肠道、呼吸道以及皮肤软组织、腹腔、骨关节等感染的治疗[9-10]。……