天然来源抗真菌药物的研究进展  

Research progress of antifungal drugs from natural sources

作　　者：初芍洁 郑岩 苏霜霜 吴雪松 闫闳 陈少欣 王宏博 CHU Shao-jie;ZHENG Yan;SU Shuang-shuang;WU Xue-song;YAN Hong;CHENShao-xin;WANG Hong-bo(National Key Laboratory of Lead Druggability Research,China State Institute of Pharmaceutical Industry,Shanghai 201203,China)

机构地区：[1]中国医药工业研究总院,先导物成药性研究全国重点实验室,上海201203

出　　处：《药学学报》2025年第1期48-57,共10页Acta Pharmaceutica Sinica

基　　金：先导物成药性研究全国重点实验室项目(NKLYT2023009);科技部国家重点研发计划“绿色生物制造”项目(2021YFC2102100);上海启明星培育(扬帆专项)项目(23YF1445800)。

摘　　要：随着免疫功能受损患者数量的增加及真菌耐药性的产生,人类感染致命真菌的风险也在不断增加。真菌和人类都属于真核生物,因此确定抗真菌药物研发的独特靶点较为困难。此外,目前现有的抗真菌药物在实际应用中受到毒性、药物相互作用和耐药性等多方面的限制,从而导致真菌感染的发病率和致命率的不断提高。因此,开发新型抗真菌药物已迫在眉睫。利用来自天然来源的微生物发酵产物作为先导化合物的半合成技术,由于其反应步骤少、易于操作的优点成为目前抗真菌药物结构改造中使用最多的方法。本文将介绍目前临床使用的天然来源的抗真菌药物的现状,以及新型半合成抗真菌药物研发的最新进展,并对其作用机制、结构修饰及优缺点进行总结,为后续新型抗真菌药物的开发提供参考。As the number of patients with compromised immune function increases and fungal resistance develops,so does the risk of contracting deadly fungi in humans.Both fungi and humans are eukaryotes,so identifying unique targets for antifungal drug development is difficult.In addition,the existing antifungal drugs are limited by toxicity,drug interaction and drug resistance in practical application,which leads to the increasing incidence and fatal rate of fungal infections.Therefore,it is urgent to develop new antifungal drugs.The semi-synthetic technology using microbial fermentation products from natural sources as lead compounds has become the most used method in structural modification of antifungal drugs due to its advantages of few reaction steps and easy operation.This paper will introduce the current status of natural antifungal drugs in clinical use,as well as the latest progress in the research and development of new semi-synthetic antifungal drugs,and summarize their mechanism of action,structural modifications,advantages and disadvantages,so as to provide reference for the subsequent development of new antifungal drugs.

关 键 词：抗真菌药物 天然产物 先导化合物 半合成技术 

分 类 号：R914[医药卫生—药物化学]