Department of Chemistry, School of Advanced Sciences (SAS), Vellore Institute of Technology, Vellore 632014, India.
Drug Discovery Unit (DDU), Centre for Biomaterials, Cellular and Molecular Theranostics (CBCMT), Vellore Institute of Technology, Vellore 632014, India.
ACS Infect Dis. 2024 Aug 9;10(8):2448-2466. doi: 10.1021/acsinfecdis.4c00046. Epub 2024 Jun 21.
Fungi pose a global threat to humankind due to the increasing emergence of multi-drug-resistant fungi. There is a rising incidence of invasive fungal infections. Due to the structural complexity of fungal cell membranes, only a few classes of antifungal agents are effective and have been approved by the U.S. FDA. Hence, researchers globally are focusing on developing novel strategies to cure fungal infections. One of the potential strategies is the "Trojan horse" approach, which uses the siderophore-mediated iron acquisition (SIA) system to scavenge iron to deliver potent antifungal agents for therapeutics and diagnostics. These siderophore conjugates chelate to iron and are taken up through siderophore-iron transporters, which are overexpressed exclusively on microbes such as bacteria or fungi, but not mammalian cells. Our comprehensive review delves into recent advancements in the design of siderophore-conjugated antifungal agents to gain fungal cell entry. Notably, our focus extends to unraveling the intricate relationship between the structure of natural siderophores or siderophore-like molecules and the resulting antifungal activity. By exploring these design strategies, we aim to contribute to the ongoing discourse on combating drug-resistant fungal infections and advancing the landscape of antifungal theranostics.
由于多药耐药真菌的不断出现，真菌对人类构成了全球性威胁。侵袭性真菌感染的发病率正在上升。由于真菌细胞膜的结构复杂，只有少数几类抗真菌药物有效，并已获得美国 FDA 的批准。因此，全球研究人员都专注于开发治疗真菌感染的新策略。一种潜在的策略是“特洛伊木马”方法，该方法利用铁摄取的铁载体介导（SIA）系统来获取铁，以输送有效的抗真菌药物进行治疗和诊断。这些铁载体缀合物与铁螯合，并通过铁载体-铁转运蛋白摄取，这些转运蛋白仅在细菌或真菌等微生物中过度表达，而不在哺乳动物细胞中表达。我们的综合评论深入探讨了设计用于获得真菌细胞进入的铁载体缀合抗真菌剂的最新进展。值得注意的是，我们的重点还在于揭示天然铁载体或类铁载体分子的结构与抗真菌活性之间的复杂关系。通过探索这些设计策略，我们旨在为对抗耐药真菌感染和推进抗真菌治疗学领域的发展做出贡献。
