State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China.
Key Laboratory for Ultrafine Materials of Ministry of Education, Frontiers Science Center for Materiobiology and Dynamic Chemistry, Research Center for Biomedical Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai, 200237, China.
Adv Sci (Weinh). 2022 May;9(14):e2104871. doi: 10.1002/advs.202104871. Epub 2022 Mar 20.
Potent and selective antifungal agents are urgently needed due to the quick increase of serious invasive fungal infections and the limited antifungal drugs available. Microbial metabolites have been a rich source of antimicrobial agents and have inspired the authors to design and obtain potent and selective antifungal agents, poly(DL-diaminopropionic acid) (PDAP) from the ring-opening polymerization of β-amino acid N-thiocarboxyanhydrides, by mimicking ε-poly-lysine. PDAP kills fungal cells by penetrating the fungal cytoplasm, generating reactive oxygen, and inducing fungal apoptosis. The optimal PDAP displays potent antifungal activity with minimum inhibitory concentration as low as 0.4 µg mL against Candida albicans, negligible hemolysis and cytotoxicity, and no susceptibility to antifungal resistance. In addition, PDAP effectively inhibits the formation of fungal biofilms and eradicates the mature biofilms. In vivo studies show that PDAP is safe and effective in treating fungal keratitis, which suggests PDAPs as promising new antifungal agents.
由于严重侵袭性真菌感染的迅速增加和可用的抗真菌药物有限，因此迫切需要有效且选择性高的抗真菌药物。微生物代谢产物一直是抗菌药物的丰富来源，这启发作者通过模拟ε-聚赖氨酸，从β-氨基酸 N-硫代碳酰亚胺的开环聚合反应中设计并获得了有效的、选择性高的抗真菌剂聚（DL-二氨基丙酸）（PDAP）。PDAP 通过穿透真菌细胞质、产生活性氧和诱导真菌细胞凋亡来杀死真菌细胞。最佳 PDAP 对白色念珠菌的最小抑菌浓度低至 0.4μg/mL，表现出很强的抗真菌活性，几乎没有溶血和细胞毒性，也不易产生抗真菌耐药性。此外，PDAP 还能有效抑制真菌生物膜的形成并消除成熟的生物膜。体内研究表明，PDAP 治疗真菌性角膜炎安全有效，这表明 PDAP 有望成为新的抗真菌药物。
