Southwell James W, Black Conor M, Duhme-Klair Anne-Kathrin
Department of Chemistry, University of York, Heslington, North Yorkshire, YO10 5DD, UK.
ChemMedChem. 2021 Apr 8;16(7):1063-1076. doi: 10.1002/cmdc.202000806. Epub 2020 Dec 10.
The field of antibacterial siderophore conjugates, referred to as Trojan Horse antibacterials, has received increasing attention in recent years, driven by the rise of antimicrobial resistance. Trojan Horse antibacterials offer an opportunity to exploit the specific pathways present in bacteria for active iron uptake, potentially allowing the drugs to bypass membrane-associated resistance mechanisms. Hence, the Trojan Horse approach might enable the redesigning of old antibiotics and the development of antibacterials that target specific pathogens. Critical parts of evaluating such Trojan Horse antibacterials and improving their design are the quantification of their bacterial uptake and the identification of the pathways by which this occurs. In this minireview, we highlight a selection of the biological and chemical methods used to study the uptake of Trojan Horse antibacterials, exemplified with case studies, some of which have led to drug candidates in clinical development or approved antibiotics.
抗菌铁载体缀合物领域，即所谓的“特洛伊木马”抗菌剂，近年来受到了越来越多的关注，这是由抗菌药物耐药性的增加所驱动的。“特洛伊木马”抗菌剂提供了一个利用细菌中存在的特定途径进行活性铁摄取的机会，这有可能使药物绕过与膜相关的耐药机制。因此，“特洛伊木马”方法可能有助于重新设计旧抗生素，并开发针对特定病原体的抗菌剂。评估此类“特洛伊木马”抗菌剂并改进其设计的关键部分是对其细菌摄取量的量化以及对摄取发生途径的识别。在本综述中，我们重点介绍了一些用于研究“特洛伊木马”抗菌剂摄取的生物学和化学方法，并通过案例研究进行了举例说明，其中一些案例已促成了处于临床开发阶段的候选药物或已获批的抗生素。
