Mehta Devashish, Saini Varsha, Bajaj Avinash
Laboratory of Nanotechnology and Chemical Biology, Regional Centre for Biotechnology Faridabad-121001 Haryana India
RSC Med Chem. 2023 Jun 26;14(9):1603-1628. doi: 10.1039/d3md00151b. eCollection 2023 Sep 19.
Fungal infections cause severe and life-threatening complications especially in immunocompromised individuals. Antifungals targeting cellular machinery and cell membranes including azoles are used in clinical practice to manage topical to systemic fungal infections. However, continuous exposure to clinically used antifungal agents in managing the fungal infections results in the development of multi-drug resistance adapting different kinds of intrinsic and extrinsic mechanisms. The unique chemical composition of fungal membranes presents attractive targets for antifungal drug discovery as it is difficult for fungal cells to modify the membrane targets for emergence of drug resistance. Here, we discussed available antifungal drugs with their detailed mechanism of action and described different antifungal resistance mechanisms. We further emphasized structure-activity relationship studies of membrane-targeting antifungal agents, and classified membrane-targeting antifungal agents on the basis of their core scaffold with detailed pharmacological properties. This review aims to pique the interest of potential researchers who could explore this interesting and intricate fungal realm.
真菌感染会引发严重且危及生命的并发症，尤其是在免疫功能低下的个体中。针对细胞机制和细胞膜的抗真菌药物（包括唑类）在临床实践中用于治疗局部和全身性真菌感染。然而，在治疗真菌感染时持续接触临床使用的抗真菌药物会导致多重耐药性的产生，其通过适应不同类型的内在和外在机制来实现。真菌细胞膜独特的化学成分使其成为抗真菌药物研发的有吸引力的靶点，因为真菌细胞难以修饰膜靶点以产生耐药性。在此，我们讨论了现有的抗真菌药物及其详细的作用机制，并描述了不同的抗真菌耐药机制。我们进一步强调了膜靶向抗真菌剂的构效关系研究，并根据其核心骨架对膜靶向抗真菌剂进行了分类，并详细阐述了其药理特性。本综述旨在激发潜在研究人员的兴趣，他们可能会探索这个有趣而复杂的真菌领域。
