Department of Medicinal Chemistry, School of Pharmacy, Second Military Medical University (Naval Medical University), 325 Guohe Road, Shanghai 200433, China.
Department of Medicinal Chemistry, School of Pharmacy, Second Military Medical University (Naval Medical University), 325 Guohe Road, Shanghai 200433, China.
Adv Drug Deliv Rev. 2023 Jun;197:114819. doi: 10.1016/j.addr.2023.114819. Epub 2023 Apr 4.
Invasive fungal infections (IFIs) are emerging as a serious threat to public health and are associated with high incidence and mortality. IFIs also represent a frequent complication in patients with cancer who are undergoing chemotherapy. However, effective and safe antifungal agents remain limited, and the development of severe drug resistance further undermines the efficacy of antifungal therapy. Therefore, there is an urgent need for novel antifungal agents to treat life-threatening fungal diseases, especially those with new mode of action, favorable pharmacokinetic profiles, and anti-resistance activity. In this review, we summarize new antifungal targets and target-based inhibitor design, with a focus on their antifungal activity, selectivity, and mechanism. We also illustrate the prodrug design strategy used to improve the physicochemical and pharmacokinetic profiles of antifungal agents. Dual-targeting antifungal agents offer a new strategy for the treatment of resistant infections and cancer-associated fungal infections.
侵袭性真菌感染（IFI）正在成为严重威胁公众健康的因素，其发病率和死亡率都很高。IFI 也是化疗癌症患者经常发生的并发症。然而，有效的和安全的抗真菌药物仍然有限，严重的耐药性的发展进一步削弱了抗真菌治疗的疗效。因此，迫切需要新型抗真菌药物来治疗危及生命的真菌感染，特别是那些具有新作用模式、良好的药代动力学特征和抗耐药性的药物。在这篇综述中，我们总结了新的抗真菌靶点和基于靶点的抑制剂设计，重点介绍了它们的抗真菌活性、选择性和作用机制。我们还说明了前药设计策略，用于改善抗真菌药物的理化和药代动力学特性。双重靶向抗真菌药物为治疗耐药感染和癌症相关真菌感染提供了一种新策略。
