Jamzivar Fatemehsadat, Shams-Ghahfarokhi Masoomeh, Khoramizadeh Mansoor, Yousefi Niloufar, Gholami-Shabani Mohammadhassan, Razzaghi-Abyaneh Mehdi
Department of Mycology, Pasteur Institute of Iran, Tehran, Iran.
Department of Mycology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Iran J Microbiol. 2019 Dec;11(6):448-459.
Over the past decades, the incidence of life-threatening fungal infections has increased dramatically in particular among patients with hampered immune function. Fungal infections cause around 1.5 million deaths annually, superior to malaria and tuberculosis. With respect to high toxicity, narrow spectrum of activity and drug resistance to current antifungals, there is an urgent need to discover novel leads from molecules of natural origin especially those derived from plants and microorganisms for antifungal drug discovery. Among antifungal drugs introduced into the clinic, those affecting ergosterol biosynthesis are still superior to other classes and the vital role of ergosterol in fungal growth and development. This review highlights current knowledge about available antifungal agents and further issues on antifungal drug discovery from compounds of natural origin which affect ergosterol biosynthesis. Special attention is made to the fungal sterol C24-methyltransferase (SMT), a crucial enzyme in ergosterol biosynthesis pathway as a novel target for rational drug design.
在过去几十年中，危及生命的真菌感染的发生率急剧上升，尤其是在免疫功能受损的患者中。真菌感染每年导致约150万人死亡，超过疟疾和结核病。鉴于目前抗真菌药物的高毒性、窄活性谱和耐药性，迫切需要从天然来源的分子中发现新的先导物，特别是那些来自植物和微生物的分子，用于抗真菌药物的研发。在引入临床的抗真菌药物中，那些影响麦角甾醇生物合成的药物仍然优于其他类别，以及麦角甾醇在真菌生长和发育中的重要作用。本综述重点介绍了有关现有抗真菌药物的当前知识，以及从影响麦角甾醇生物合成的天然来源化合物中发现抗真菌药物的进一步问题。特别关注真菌甾醇C24-甲基转移酶（SMT），它是麦角甾醇生物合成途径中的一种关键酶，作为合理药物设计的新靶点。
