Development of Gallium(III) as an Antimicrobial Drug Targeting Pathophysiologic Iron Metabolism of Human Pathogens

被引:6
作者
Scott, Zachary W. [1 ]
Choi, Seoung-ryoung [1 ]
Britigan, Bradley E. [1 ,2 ,3 ,4 ]
Narayanasamy, Prabagaran [1 ]
机构
[1] Univ Nebraska Med Ctr, Coll Med, Dept Pathol & Microbiol, Omaha, NE 68198 USA
[2] Univ Nebraska Med Ctr, Coll Med, Dept Internal Med, Omaha, NE 68198 USA
[3] Vet Affairs Med Ctr Nebraska Western Iowa, Dept Internal Med, Omaha, NE 68105 USA
[4] Vet Affairs Med Ctr Nebraska Western Iowa, Res Serv, Omaha, NE 68105 USA
来源
ACS INFECTIOUS DISEASES | 2023年 / 9卷 / 04期
关键词
gallium; iron; heme; metabolism; inhibitor; drug candidate; RESISTANT PSEUDOMONAS-AERUGINOSA; IN-VITRO; MYCOBACTERIUM-AVIUM; VIRULENCE FACTORS; NITRATE; ACQUISITION; TRANSFERRIN; INFECTION; MALTOLATE; GROWTH;
D O I
10.1021/acsinfecdis.3c00050
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
The treatment of infections is becoming more difficult due to emerging resistance of pathogens to existing drugs. As such, alternative druggable targets, particularly those that are essential for microbe viability and thus make it harder to develop resistance, are desperately needed. In turn, once identified, safe and effective agents that disrupt these targets must be developed. Microbial acquisition and use of iron is a promising novel target for antimicrobial drug development. In this Review we look at the various facets of iron metabolism critical to human infection with pathogenic microbes and the various ways in which it can be targeted, altered, disrupted, and taken advantage of to halt or eliminate microbial infections. Although a variety of agents will be touched upon, the primary focus will be on the potential use of one or more gallium complexes as a new class of antimicrobial agents. In vitro and in vivo data on the activity of gallium complexes against a variety of pathogens including ESKAPE pathogens, mycobacteria, emerging viruses, and fungi will be discussed in detail, as well as pharmacokinetics, novel formulations and delivery approaches, and early human clinical results.
引用
收藏
页码:716 / 738
页数:23
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