Xiong Juan, Lu Hui, Jiang Yuanying
Department of Pharmacy, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200092, China.
ACS Infect Dis. 2025 Feb 14;11(2):305-322. doi: 10.1021/acsinfecdis.4c00657. Epub 2025 Jan 3.
The emergence of azole resistance and tolerance in pathogenic fungi has emerged as a significant public health concern, emphasizing the urgency for innovative strategies to bolster the efficacy of azole-based treatments. Drug repurposing stands as a promising and practical avenue for advancing antifungal therapy, with the potential for swift clinical translation. This review offers a comprehensive overview of azole synergistic agents uncovered through drug repurposing strategies, alongside an in-depth exploration of the mechanisms by which these agents augment azole potency. Drawing from these mechanisms, we delineate strategies aimed at enhancing azole effectiveness, such as inhibiting efflux pumps to elevate azole concentrations within fungal cells, intensifying ergosterol synthesis inhibition, mitigating fungal cell resistance to azoles, and disrupting biological processes extending beyond ergosterol synthesis. This review is beneficial for the development of these potentiators, as it meticulously examines instances and provides nuanced discussions on the mechanisms underlying the progression of azole potentiators through drug repurposing strategies.
致病真菌中唑类耐药性和耐受性的出现已成为一个重大的公共卫生问题，凸显了采取创新策略提高基于唑类治疗效果的紧迫性。药物重新利用是推进抗真菌治疗的一个有前景且切实可行的途径，具有迅速临床转化的潜力。本综述全面概述了通过药物重新利用策略发现的唑类协同剂，并深入探讨了这些药剂增强唑类效力的机制。基于这些机制，我们阐述了旨在提高唑类有效性的策略，例如抑制外排泵以提高真菌细胞内的唑类浓度、加强麦角甾醇合成抑制、减轻真菌细胞对唑类的耐药性，以及破坏超越麦角甾醇合成的生物过程。本综述对这些增效剂的开发有益处，因为它细致地研究了实例，并对通过药物重新利用策略推进唑类增效剂的机制进行了细致入微的讨论。
