A Review of Antibacterial Candidates with New Modes of Action.

IF 4 2区医学 Q2 CHEMISTRY, MEDICINAL

ACS Infectious Diseases Pub Date : 2024-10-11 Epub Date: 2024-07-17 DOI:10.1021/acsinfecdis.4c00218

Mark S Butler, Waldemar Vollmer, Emily C A Goodall, Robert J Capon, Ian R Henderson, Mark A T Blaskovich

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Abstract

There is a lack of new antibiotics to combat drug-resistant bacterial infections that increasingly threaten global health. The current pipeline of clinical-stage antimicrobials is primarily populated by "new and improved" versions of existing antibiotic classes, supplemented by several novel chemical scaffolds that act on traditional targets. The lack of fresh chemotypes acting on previously unexploited targets (the "holy grail" for new antimicrobials due to their scarcity) is particularly unfortunate as these offer the greatest opportunity for innovative breakthroughs to overcome existing resistance. In recognition of their potential, this review focuses on this subset of high value antibiotics, providing chemical structures where available. This review focuses on candidates that have progressed to clinical trials, as well as selected examples of promising pioneering approaches in advanced stages of development, in order to stimulate additional research aimed at combating drug-resistant infections.

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具有新作用模式的抗菌候选药物综述。

抗药性细菌感染日益威胁着全球健康，目前缺乏新型抗生素来应对这种感染。目前处于临床阶段的抗菌药物主要是现有抗生素类别的 "新改良 "版本，并辅以一些作用于传统靶点的新型化学支架。尤其令人遗憾的是，缺乏作用于以前未开发靶点（由于其稀缺性，是新型抗菌药物的 "圣杯"）的新化学类型，因为这些靶点为克服现有抗药性提供了最大的创新突破机会。鉴于这些抗生素的潜力，本综述将重点关注这部分高价值抗生素，并提供可用的化学结构。本综述重点关注已进入临床试验阶段的候选药物，以及处于后期开发阶段、前景广阔的开创性方法的部分实例，以促进更多旨在抗击耐药性感染的研究。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

ACS Infectious Diseases CHEMISTRY, MEDICINALINFECTIOUS DISEASES&nb-INFECTIOUS DISEASES

CiteScore

9.70

自引率

3.80%

发文量

213

期刊介绍： ACS Infectious Diseases will be the first journal to highlight chemistry and its role in this multidisciplinary and collaborative research area. The journal will cover a diverse array of topics including, but not limited to: * Discovery and development of new antimicrobial agents — identified through target- or phenotypic-based approaches as well as compounds that induce synergy with antimicrobials. * Characterization and validation of drug target or pathways — use of single target and genome-wide knockdown and knockouts, biochemical studies, structural biology, new technologies to facilitate characterization and prioritization of potential drug targets. * Mechanism of drug resistance — fundamental research that advances our understanding of resistance; strategies to prevent resistance. * Mechanisms of action — use of genetic, metabolomic, and activity- and affinity-based protein profiling to elucidate the mechanism of action of clinical and experimental antimicrobial agents. * Host-pathogen interactions — tools for studying host-pathogen interactions, cellular biochemistry of hosts and pathogens, and molecular interactions of pathogens with host microbiota. * Small molecule vaccine adjuvants for infectious disease. * Viral and bacterial biochemistry and molecular biology.