Department of Biology and Biotechnology "Lazzaro Spallanzani", University of Pavia, Via A. Ferrata 9, 27100 Pavia, Italy.
Department of Pharmaceutical Sciences, University of Milan, Via L. Mangiagalli 25, 20133 Milano, Italy.
Int J Mol Sci. 2023 Mar 24;24(7):6181. doi: 10.3390/ijms24076181.
The emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) infections is one of the most crucial challenges currently faced by the scientific community. Developments in the fundamental understanding of their underlying mechanisms may open new perspectives in drug discovery. In this review, we conducted a systematic literature search in PubMed, Web of Science, and Scopus, to collect information on innovative strategies to hinder iron acquisition in bacteria. In detail, we discussed the most interesting targets from iron uptake and metabolism pathways, and examined the main chemical entities that exhibit anti-infective activities by interfering with their function. The mechanism of action of each drug candidate was also reviewed, together with its pharmacodynamic, pharmacokinetic, and toxicological properties. The comprehensive knowledge of such an impactful area of research will hopefully reflect in the discovery of newer antibiotics able to effectively tackle the antimicrobial resistance issue.
多药耐药（MDR）和广泛耐药（XDR）感染的出现是科学界目前面临的最关键挑战之一。对其潜在机制的基础理解的发展可能会为药物发现开辟新的视角。在本综述中，我们在 PubMed、Web of Science 和 Scopus 中进行了系统的文献检索，以收集有关阻碍细菌中铁摄取的创新策略的信息。详细地，我们讨论了来自铁摄取和代谢途径的最有趣的靶点，并研究了通过干扰其功能表现出抗感染活性的主要化学实体。还回顾了每个候选药物的作用机制及其药效学、药代动力学和毒理学特性。对这一有影响力的研究领域的全面了解有望反映在发现能够有效解决抗微生物药物耐药性问题的新型抗生素方面。
