喹诺酮杂合体的抗耐甲氧西林金葡菌活性研究进展  

Recent progress of quinolone hybrids with antibacterial potential against methicillin-resistant Staphylococcus aureus

作　　者：王林硕 李晓 王宝君[1] Wang Linshuo;Li Xiao;Wang Baojun(Shijiazhuang Medical College,Shijiazhuang 050599;Handan Maternal and Child Health Care Hospital,Handan 056000)

机构地区：[1]石家庄医学高等专科学校,石家庄050599 [2]邯郸市妇幼保健院,邯郸056000

出　　处：《中国抗生素杂志》2023年第9期990-998,共9页Chinese Journal of Antibiotics

基　　金：河北省卫健委课题(No.20201430)。

摘　　要：耐甲氧西林金葡菌(MRSA)是引起院内和社区感染的重要病原菌,高发病率与致死率使得其位居感染病原菌之首。MRSA是多重耐药致病菌,目前已对包括万古霉素在内的几乎所有抗生素产生了不同程度的耐药性。因此,开发新型抗MRSA药物刻不容缓。喹诺酮尤其是氟喹诺酮是临床上广泛使用的一类广谱抗菌药,对包括某些MRSA在内的多种致病菌引起的感染具有良好的疗效。杂合体具有多个药效团可同时作用于不同的药物靶点,故杂合体策略是克服耐药性的常用策略。喹诺酮与其它抗MRSA药效团相结合所得的杂合体可发挥协同作用,寻找新型抗MRSA药物的潜力分子。近年来,药物化学家设计合成评价了多个系列喹诺酮杂合体的抗MRSA活性,发现了多个具有进一步研究价值的潜在化合物。本文将着重介绍2015—2022年间所发展的具有抗MRSA活性的喹诺酮杂合体的研究进展,并归纳构-效关系,为进一步合理设计此类杂合体提供一定的理论支持。Methicillin-resistant Staphylococcus aureus(MRSA)strains,the most common pathogens in hospital and community,remains a leading cause of bacterial infections worldwide due to the high mortality and morbidity.MRSA are multi-drug resistant pathogens and have already developed resistance to almost all antibiotics including vancomycin,necessitating the development of novel agents for combating these superbugs.Quinolones,especially fluoroquinolones,are broad-spectrum antibacterial agents widely applied in clinical practice and demonstrated excellent curative effect on infections caused by diverse pathogenic bacteria,including some MRSA.Hybrid molecules possess multiple pharmacophores that can act on different drug targets simultaneously,so hybridization is a promising strategy to overcome drug resistance.Combination of the quinolone moiety with other pharmacophores against MRSA has the potential to exert synergistic effect,thus quinolone hybrids are useful templates for searching for new anti-MRSA drugs.In this review,the anti-MRSA potential and the structure-activity relationship of quinolone hybrids are discussed,which will provide a reference for further research.

关 键 词：喹诺酮 杂合体 抗菌 耐甲氧西林金葡菌 构-效关系 

分 类 号：R978.1[医药卫生—药品]