Polymeric Iron Chelator with Enhanced Iron Affinity as a Broad-Spectrum Antifungal Agent

被引:3
|
作者
Qian, Jian [1 ]
Wiederhold, Nathan P. [2 ,3 ]
Patterson, Thomas [3 ,4 ]
Patterson, Hoja [2 ]
Berkland, Cory J. [1 ]
机构
[1] Univ Kansas, Dept Pharmaceut Chem, Lawrence, KS 66047 USA
[2] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol & Lab Med, San Antonio, TX 78229 USA
[3] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA
[4] South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA
基金
美国国家卫生研究院;
关键词
antifungal drug; polymeric iron chelator; broad-spectrum antifungal effect; siderophore; reductive iron assimilation; SIDEROPHORES; TRANSPORT;
D O I
10.1021/acsapm.1c01269
中图分类号
T [工业技术];
学科分类号
08 ;
摘要
Developing broad-spectrum antifungal drugs represents a pressing need for reducing the global burden of fungal infections. We took advantage of the conformational stability effect to develop a high-avidity polymeric iron chelator, 2,3-dihydroxybenzoic acid-conjugated poly(L-lysine hydrochloride) (PLL-DHBA), which exhibited a stronger iron affinity than typical siderophores produced by fungi. Minimum inhibitory concentration studies against 8 types of fungi including 37 strains showed that the PLL-DHBA iron chelator exhibited a broad-spectrum antifungal effect. Moreover, PLL-DHBA was even more potent than some traditional antifungal drugs for certain drug-resistant fungi.
引用
收藏
页码:6034 / 6039
页数:6
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