抗真菌药物：作用机制与耐药性，已上市及新型药物

Antifungals: mechanism of action and resistance, established and novel drugs.

作者信息

Georgopapadakou N H

机构信息

DuPont Pharmaceuticals Research Laboratories, Experimental Station, E400/3442, Rt 141 & Henry Clay Road, PO Box 80400, Wilmington DE 19880-0400, USA.

出版信息

Curr Opin Microbiol. 1998 Oct;1(5):547-57. doi: 10.1016/s1369-5274(98)80087-8.

DOI:10.1016/s1369-5274(98)80087-8

PMID:10066533

Abstract

Serious fungal infections, caused mostly by opportunistic species, are increasingly common in immunocompromised and other vulnerable patients. The use of antifungal drugs, primarily azoles and polyenes, has increased in parallel. Yet, established agents do not satisfy the medical need completely: azoles are fungistatic and vulnerable to resistance, whereas polyenes cause serious host toxicity. Drugs in clinical development include echinocandins, pneumocandins, and improved azoles. Promising novel agents in preclinical development include several inhibitors of fungal protein, lipid and cell wall syntheses. Recent advances in fungal genomics, combinatorial chemistry, and high-throughput screening may accelerate the antifungal discovery process.

摘要

严重的真菌感染主要由机会性真菌引起，在免疫功能低下及其他易感染患者中越来越常见。抗真菌药物（主要是唑类和多烯类）的使用也相应增加。然而，现有的药物并不能完全满足医疗需求：唑类药物具有抑菌作用且易产生耐药性，而多烯类药物会对宿主造成严重毒性。处于临床开发阶段的药物包括棘白菌素、肺胞菌素和改良的唑类药物。处于临床前开发阶段的有前景的新型药物包括几种真菌蛋白质、脂质和细胞壁合成抑制剂。真菌基因组学、组合化学和高通量筛选方面的最新进展可能会加速抗真菌药物的研发进程。