期刊
ACS INFECTIOUS DISEASES
卷 6, 期 9, 页码 2532-2541出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsinfecdis.0c00568
关键词
siderophores; antibiotics; drug design; radiolabeling; bioinorganic chemistry
资金
- UK Engineering and Physical Sciences Research Council (EPSRC) [EP/K503216/1, EP/L505122/1, EP/N509802/1]
- University of York, Department of Chemistry
- EPSRC [EP/T007338/1, EP/L024829/1]
- EPSRC [EP/L024829/1] Funding Source: UKRI
A novel ciprofloxacin-siderophore Trojan Horse antimicrobial was prepared by incorporating key design features of salmochelin, a stealth siderophore that evades mammalian siderocalin capture via its glycosylated catechol units. Assessment of the antimicrobial activity of the conjugate revealed that attachment of the salmochelin mimic resulted in decreased potency, compared to ciprofloxacin, against two Escherichia coli strains, K12 and Nissle 1917, in both iron replete and deplete conditions. This observation could be attributed to a combination of reduced DNA gyrase inhibition, as confirmed by in vitro DNA gyrase assays, and reduced bacterial uptake. Uptake was monitored using radiolabeling with iron-mimetic Ga-67(3+), which revealed limited cellular uptake in E. coli K12. In contrast, previously reported staphyloferrin-based conjugates displayed a measurable uptake in analogous Ga-67(3+) labeling studies. These results suggest that, in the design of Trojan Horse antimicrobials, the choice of siderophore and the nature and length of the linker remain a significant challenge.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据