Faculty of Pharmacy, School of Food and Biological Engineering, Shaanxi University of Science and Technology, Xuefu Middle Road, Xi'an 710021, People's Republic of China.
Department of Medicinal Chemistry and Pharmaceutical Analysis, School of Pharmacy, Fourth Military Medical University, 169 Changle West Road, Xi'an 710032, People's Republic of China.
J Med Chem. 2020 Nov 12;63(21):12429-12459. doi: 10.1021/acs.jmedchem.0c00748. Epub 2020 Aug 4.
Due to the limit of available treatments and the emergence of drug resistance in the clinic, invasive fungal infections are an intractable problem with high morbidity and mortality. The cell wall, as a fungi-specific structure, is an appealing target for the discovery and development of novel and low-toxic antifungal agents. In an attempt to accelerate the discovery of novel cell wall targeted drugs, this Perspective will provide a comprehensive review of the progress made to date on the development of fungal cell wall inhibitors. Specifically, this review will focus on the targets, discovery process, chemical structures, antifungal activities, and structure-activity relationships. Although two types of cell wall antifungal agents are clinically available or in clinical trials, it is still a long way for the other cell wall targeted inhibitors to be translated into clinical applications. Future efforts should be focused on the identification of inhibitors against novel conserved cell wall targets.
由于现有治疗方法的局限性和临床耐药性的出现，侵袭性真菌感染是一个发病率和死亡率都很高的棘手问题。细胞壁作为真菌特有的结构，是发现和开发新型低毒抗真菌药物的一个有吸引力的靶点。为了加速新型细胞壁靶向药物的发现，本观点将全面综述真菌细胞壁抑制剂的研究进展。具体而言，本综述将重点介绍靶点、发现过程、化学结构、抗真菌活性和构效关系。尽管已有两种类型的细胞壁抗真菌药物在临床上可用或处于临床试验阶段，但其他细胞壁靶向抑制剂要转化为临床应用还有很长的路要走。未来的工作应集中于鉴定针对新型保守细胞壁靶标的抑制剂。
