抗真菌药物作用靶点机理及新药研发进展

抗真菌药物的大量使用导致真菌耐药性的增加,影响了病人的康复甚至威胁生命。开发安全、高效、广谱的新型抗真菌药物尤为重要。本文首先阐述了抗真菌药物的作用机理以及相应作用靶点。作用机理主要分为抑制真菌细胞壁合成与影响细胞膜功能2种),作用靶点(包括细胞壁中的β-葡聚糖合成酶、几丁质合成酶、甘露聚糖及其复合物等,和细胞膜中的脂类、麦角甾醇及其相关酶等)。针对新型抗真菌药物的研发亟待提高速率的现状,本文综述了新型抗真菌药物的发现、发展途径及相关药物分析方法,从海洋资源的开发、中草药提取开发、常规方法的改进,到新兴的计算机辅助药物设计等。综合运用以上方法,结合微量、灵敏、快速药物分析技术,有望推动新型抗真菌药物研发的提速。

The excessive use of antifungal drugs has greatly increased fungal resistance, threatening patients, recovery and lives.Therefore, it becomes more imperative to discover and develop efficient, safe, low-toxic and broad-spectrum antifungal drugs.In this paper, an elaborate review on the research advances in antifungal agents is given, especially in their action mechanisms, namely inhibiting the biosynthesis of cell wall and disturbing the functions of cell membranes.The relevant action targets include β-1, 3-glucan synthase, chitin synthase, mannan and its complexes as well as lipids, ergosterols and related enzymes in cell membrane.Focusing on the current situation that the development of novel antifungal drugs needs to speed up, the paper reviews several ways of discovering and developing novel drugs and relevant pharmaceutical analytical methods, such as the development of marine resource and Chinese medicines, the improvement of traditional methods and the emerging computer-aided drug design.Through comprehensive utilization of these methods accompanied by the trace, sensitive and rapid pharmaceutical analytical technology, great progress is promisingly to be made in the development of novel antifungal drugs in the near future.