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鉴定具有抗新兴真菌病原体的抗真菌活性的非专利化合物。

Identification of Off-Patent Compounds That Present Antifungal Activity Against the Emerging Fungal Pathogen .

机构信息

Mycology Reference Laboratory, National Centre for Microbiology, Instituto de Salud Carlos III, Madrid, Spain.

Laboratório de Micologia Clínica, Departamento de Análises Clínicas, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista (UNESP), Araraquara, Brazil.

出版信息

Front Cell Infect Microbiol. 2019 Apr 2;9:83. doi: 10.3389/fcimb.2019.00083. eCollection 2019.

Abstract

is an emerging fungal pathogen of great concern among the scientific community because it is causing an increasing number of hospital outbreaks of difficult management worldwide. In addition, isolates from this species frequently present reduced susceptibility to azole and echinocandin drugs. For this reason, it is necessary to develop new antifungal strategies to better control the disease caused by this yeast. In this work, we screened drugs from the Prestwick chemical library, which contains 1,280 off-patent compounds that are already approved by the Food and Drug Administration, with the aim of identifying molecules with antifungal activity against . In an initial screening, we looked for drugs that inhibited the growth of three different strains and found 27 of them which it did so. Ten active compounds were selected to test the susceptibility profile by using the EUCAST protocol. Antifungal activity was confirmed for seven drugs with MICs ranging from 0.5 to 64 mg/L. Some of these drugs were also tested in combination with voriconazole and anidulafungin at sub-inhibitory concentrations. Our results suggest synergistic interactions between suloctidil and voriconazole with fractional inhibitory concentration index (FICI) values of 0.11 to 0.5 and between ebselen and anidulafungin (FICI, 0.12 to 0.44). Our findings indicate that drug repurposing could be a viable alternative to managing infections by .

摘要

是一种新兴的真菌病原体,引起了科学界的极大关注,因为它在全球范围内导致越来越多难以管理的医院爆发。此外,该物种的分离株经常对唑类和棘白菌素类药物表现出较低的敏感性。因此,有必要开发新的抗真菌策略来更好地控制这种酵母引起的疾病。在这项工作中,我们筛选了 Prestwick 化学文库中的药物,该文库包含 1280 种已获得美国食品和药物管理局批准的非专利化合物,目的是确定对具有抗真菌活性的分子。在初步筛选中,我们寻找抑制三种不同菌株生长的药物,发现其中 27 种具有这种作用。选择了十种活性化合物根据 EUCAST 方案测试其药敏谱。七种药物的抗真菌活性得到证实,其 MIC 值范围为 0.5 至 64mg/L。其中一些药物还在亚抑菌浓度下与伏立康唑和安尼卡地平联合测试。我们的结果表明,suloctidil 与伏立康唑之间存在协同相互作用,其分数抑制浓度指数(FICI)值为 0.11 至 0.5,而 ebselen 与 anidulafungin 之间的 FICI 值为 0.12 至 0.44。我们的研究结果表明,药物再利用可能是管理感染的一种可行替代方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a92/6454888/45adb0ec4741/fcimb-09-00083-g0001.jpg

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