Liu Chun-Yue, Zhang Lu, Liu Si-Xuan, Lu Yong-Fu, Li Chang, Pei Yue-Hu
Department of Medicinal Chemistry and Natural Medicine Chemistry, College of Pharmacy, Harbin Medical University, Harbin, China.
Department of Chemistry, College of Pharmacy, Harbin Medical University, Daqing, China.
Front Pharmacol. 2024 Aug 21;15:1447450. doi: 10.3389/fphar.2024.1447450. eCollection 2024.
Human fungal pathogens could cause a broad plethora of infections in both the immunocompetent and immunocompromised host. Fungal infections have become important causes of morbidity and mortality in recent years, the current arsenal of anti-fungal therapies was restricted. Ibrexafungerp was a novel, highly bioavailable glucan synthase inhibitor formulated for both intravenous and oral administration being developed by Scynexis; it was also the first novel anti-fungal drug class approved in more than 20 years. Ibrexafungerp was one semi-synthetic derivative of enfumafungin, a natural product isolated from fungi. This review reported the discovery of enfumafungin and ibrexafungerp, their anti-fungal mechanism, summed up 63 fernane-type triterpenoids from natural products, including 49 from plants, 9 from fungi and 5 from lichen. In addition, the review summarized the progress of enzymes responsible for the biosynthesis of type II fernane triterpenoid (enfumafungin skeleton) and type I fernane triterpenoid (polytolypin skeleton). The good example kept our confidence up for searching for new leading compounds and discovering drugs from fungi.
人类真菌病原体可在免疫功能正常和免疫功能低下的宿主中引起广泛的多种感染。近年来，真菌感染已成为发病和死亡的重要原因，目前的抗真菌治疗手段有限。依布雷xafungerp是Scynexis公司研发的一种新型、生物利用度高的葡聚糖合酶抑制剂，可通过静脉和口服给药；它也是20多年来首个获批的新型抗真菌药物类别。依布雷xafungerp是恩夫马芬净的一种半合成衍生物，恩夫马芬净是一种从真菌中分离出的天然产物。本综述报道了恩夫马芬净和依布雷xafungerp的发现、它们的抗真菌机制，总结了63种天然产物中的蕨烷型三萜类化合物，其中49种来自植物，9种来自真菌，5种来自地衣。此外，该综述还总结了负责II型蕨烷三萜（恩夫马芬净骨架）和I型蕨烷三萜（多聚托利平骨架）生物合成的酶的研究进展。这个很好的例子让我们在从真菌中寻找新的先导化合物和发现药物方面充满信心。
