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抗真菌药物

Antifungal Drugs.

作者信息

Houšť Jiří, Spížek Jaroslav, Havlíček Vladimír

机构信息

Institute of Microbiology of the Czech Academy of Sciences, Vídeňská 1083, 14220 Prague, Czech Republic.

出版信息

Metabolites. 2020 Mar 12;10(3):106. doi: 10.3390/metabo10030106.

Abstract

We reviewed the licensed antifungal drugs and summarized their mechanisms of action, pharmacological profiles, and susceptibility to specific fungi. Approved antimycotics inhibit 1,3-β-d-glucan synthase, lanosterol 14-α-demethylase, protein, and deoxyribonucleic acid biosynthesis, or sequestrate ergosterol. Their most severe side effects are hepatotoxicity, nephrotoxicity, and myelotoxicity. Whereas triazoles exhibit the most significant drug-drug interactions, echinocandins exhibit almost none. The antifungal resistance may be developed across most pathogens and includes drug target overexpression, efflux pump activation, and amino acid substitution. The experimental antifungal drugs in clinical trials are also reviewed. Siderophores in the Trojan horse approach or the application of siderophore biosynthesis enzyme inhibitors represent the most promising emerging antifungal therapies.

摘要

我们回顾了已获许可的抗真菌药物,并总结了它们的作用机制、药理学特性以及对特定真菌的敏感性。已批准的抗真菌药物可抑制1,3-β-D-葡聚糖合酶、羊毛甾醇14-α-脱甲基酶、蛋白质和脱氧核糖核酸的生物合成,或螯合麦角甾醇。它们最严重的副作用是肝毒性、肾毒性和骨髓毒性。三唑类药物表现出最显著的药物相互作用,而棘白菌素类药物几乎没有。大多数病原体都可能产生抗真菌耐药性,包括药物靶点过表达、外排泵激活和氨基酸替代。我们还回顾了临床试验中的实验性抗真菌药物。特洛伊木马策略中的铁载体或铁载体生物合成酶抑制剂的应用代表了最有前景的新兴抗真菌疗法。

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