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2020 , Vol. 40 >Issue 10: 3026 - 3043

DOI: https://doi.org/10.6023/cjoc202006042

综述与进展

铁载体分子偶联抗生素药物研究进展

  • 刘君 ,
  • 侯劲松 ,
  • 孟影 ,
  • 缪志颖 ,
  • 林静 ,
  • 陈卫民
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  • 暨南大学药学院 广州 510632

收稿日期: 2020-06-21

  修回日期: 2020-08-20

  网络出版日期: 2020-08-27

基金资助

国家自然科学基金（No.81872776）资助项目.

收起

Research Progress of Antibiotics Conjugated with Siderophores

  • Liu Jun ,
  • Hou Jinsong ,
  • Meng Ying ,
  • Miao Zhiying ,
  • Lin Jing ,
  • Chen Weimin
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  • College of Pharmacy, Jinan University, Guangzhou 510632

Received date: 2020-06-21

  Revised date: 2020-08-20

  Online published: 2020-08-27

Supported by

Project supported by the National Natural Science Foundation of China (No. 81872776).

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摘要

天然铁载体是细菌分泌的一种小分子铁离子螯合剂，与铁离子螯合后可被特定的外膜受体识别并转运至胞浆内为细菌提供必需的铁.利用铁载体分子这种特性，可将药物分子与其偶联，通过细菌铁摄取系统使抗生素进入细菌从而杀死细菌，这一策略被称为“特洛伊木马”策略.2019年，第一个铁载体-抗生素偶联药物Cefiderocol被批准上市，引起许多专家和制药企业对本领域的研究兴趣.从铁载体分子的类别、不同作用机制的抗生素以及连接体的选择三个方面对铁载体分子偶联抗生素药物进行了较全面的综述，总结了铁载体-抗生素偶联物其三个组成部分分别对于新抗生素发挥抗菌作用的规律，为新型铁载体偶联抗生素药物的研发提供参考.

关键词： 抗生素; 铁载体分子; 偶联物; “特洛伊木马”策略

本文引用格式

刘君 , 侯劲松 , 孟影 , 缪志颖 , 林静 , 陈卫民 . 铁载体分子偶联抗生素药物研究进展[J]. 有机化学, 2020 , 40(10) : 3026 -3043 . DOI: 10.6023/cjoc202006042

Abstract

The natural siderophore is a class of small-molecule iron ion chelating agents secreted by bacteria, which can be recognized by specific outer membrane receptors and transported into cytoplasm to provide iron for bacteria. Using this characteristic of siderophore, antibiotics can be coupled with them and enter into bacteria through the bacterial iron uptake system. This strategy is called "Trojan horse" strategy. Recently, cefiderocol, the first siderophore-antibiotic conjugate, was approved for marketing, which has aroused accumulated interest of scientists and pharmaceutical companies in this field. This paper provides a comprehensive review of the progress in antibiotics conjugated with siderophores from three aspects:the types of siderophore molecules, antibiotics with different action mechanisms, and the role of linkers. The basic relationship between anti-bacterial activity and three moieties of this novel type of anti-bacterial agents has been revealed. This review will provide a reference for the development of new antibiotics conjugated with siderophores.

Key words： antibiotic; siderophore; conjugate; "Trojan horse" strategy

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