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评估绿原酸对氟康唑耐药 株的抗真菌作用:诱导细胞凋亡及分析可能的作用机制。

Evaluation of the antifungal effect of chlorogenic acid against strains of spp. resistant to fluconazole: apoptosis induction and analysis of the possible mechanisms of action.

机构信息

School of Pharmacy, Laboratory of Bioprospection in Antimicrobial Molecules (LABIMAN), Federal University of Ceará, Fortaleza, CE, Brazil.

Drug Research and Development Center, Federal University of Ceará, Fortaleza, CE, Brazil.

出版信息

J Med Microbiol. 2022 May;71(5). doi: 10.1099/jmm.0.001526.

DOI:10.1099/jmm.0.001526
PMID:35575783
Abstract

spp. are commensal fungal pathogens of humans, but when there is an imbalance in the microbiota, or weak host immunity, these yeasts can become pathogenic, generating high medical costs. With the increase in resistance to conventional antifungals, the development of new therapeutic strategies is necessary. This study evaluated the antifungal activity of chlorogenic acid against fluconazole-resistant strains of spp. Mechanism of action through flow cytometry and analyses, as well as molecular docking assays with ALS3 and SAP5, important proteins in the pathogenesis of associated with the adhesion process and biofilm formation. The chlorogenic acid showed antifungal activity against the strains tested, causing reduced cell viability, increased potential for mitochondrial depolarization and production of reactive oxygen species, DNA fragmentation and phosphatidylserine externalization, indicating an apoptotic process. Concerning the analysis through docking, the complexes formed between chlorogenic acid and the targets , CYP51, 1 e -B-(1,3)- demonstrated more favourable binding energy. In addition, chlorogenic acid presented significant interactions with the ALS3 active site residues of important in the adhesion process and resistance to fluconazole. Regarding molecular docking with SAP5, no significant interactions were found between chlorogenic acid and the active site of the enzyme. We concluded that chlorogenic acid has potential use as an adjuvant in antifungal therapies, due to its anti- activity and ability to interact with important drug targets.

摘要

该物种是人类共生的真菌病原体,但当微生物群落失衡或宿主免疫力较弱时,这些酵母可能会变得具有致病性,产生高昂的医疗费用。随着对传统抗真菌药物耐药性的增加,有必要开发新的治疗策略。本研究评估了绿原酸对氟康唑耐药的该物种的抗真菌活性。通过流式细胞术和分析,以及与 ALS3 和 SAP5 的分子对接试验,研究了其作用机制,ALS3 和 SAP5 是与粘附过程和生物膜形成相关的该物种发病机制中的重要蛋白。绿原酸对测试的菌株表现出抗真菌活性,导致细胞活力降低、线粒体去极化和活性氧产生增加、DNA 片段化和磷脂酰丝氨酸外翻,表明发生了凋亡过程。关于对接分析,绿原酸与靶标 CYP51、1 e -B-(1,3)-之间形成的复合物具有更有利的结合能。此外,绿原酸与 ALS3 活性位点残基的相互作用显著,ALS3 在粘附过程和对氟康唑的耐药性中很重要。关于与 SAP5 的分子对接,未发现绿原酸与酶的活性位点之间存在显著相互作用。我们得出结论,绿原酸具有作为抗真菌治疗辅助剂的潜力,因为它具有抗活性并且能够与重要的药物靶标相互作用。

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