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洗必泰作为一种针对……的强效抗真菌剂。 (原文不完整,翻译可能不太准确,完整准确翻译需补充完整原文内容)

Alexidine as a Potent Antifungal Agent Against .

作者信息

Pimentel Larissa Rodrigues, Lucini Fabiola, da Silva Gabrieli Argueiro, Simionatto Simone, Rossato Luana

机构信息

Health Sciences Research Laboratory, Federal University of Grande Dourados, Dourados, Mato Grosso do Sul 79825-070, Brazil.

出版信息

ACS Omega. 2025 Mar 20;10(12):12366-12374. doi: 10.1021/acsomega.4c11382. eCollection 2025 Apr 1.

Abstract

The increasing prevalence of infections by , particularly due to its resistance to standard antifungal therapies, represents a significant healthcare challenge. Traditional treatments often fail, emphasizing the need to explore alternative therapeutic strategies. Drug repurposing, which reevaluates existing drugs for new applications, offers a promising path. This study examines the potential of repurposing alexidine dihydrochloride as an antifungal agent against . Minimum Inhibitory Concentration (MIC) and Minimum Fungicidal Concentration (MFC) values were established using broth microdilution methods. To further assess antifungal activity, different assays were conducted, including growth inhibition, biofilm inhibition, biofilm eradication, and cell damage. Checkerboard assays were employed to study the compound's fungicidal potential and interactions with other antifungals. Additional tests, sorbitol protection assay, efflux pump inhibition, cell membrane permeability assays, and nucleotide leakage were performed. efficacy and safety were evaluated in larvae. Alexidine demonstrated fungicidal activity against , with an MIC of 0.5 μg/mL. Biofilm formation was significantly inhibited, with a reduction of 78.69%. Mechanistic studies revealed nucleotide leakage, indicating membrane impact, but no significant protein leakage was detected. , alexidine displayed a favorable safety profile, with no evidence of hemolysis or acute toxicity in the model. These findings support alexidine as a strong candidate for antifungal drug repurposing, especially for treating infections. Its efficacy in inhibiting growth and biofilm formation, combined with a positive safety profile, underscores its potential for clinical development as an antifungal therapy.

摘要

[某种真菌]感染的患病率不断上升,尤其是由于其对标准抗真菌疗法具有耐药性,这对医疗保健构成了重大挑战。传统治疗方法往往无效,这凸显了探索替代治疗策略的必要性。药物重新利用,即重新评估现有药物的新用途,提供了一条有前景的途径。本研究考察了将二盐酸阿来西定重新用作抗[某种真菌]的抗真菌剂的潜力。采用肉汤微量稀释法确定最低抑菌浓度(MIC)和最低杀菌浓度(MFC)值。为了进一步评估抗真菌活性,进行了不同的试验,包括生长抑制、生物膜抑制、生物膜根除和细胞损伤试验。采用棋盘法研究该化合物的杀菌潜力及其与其他抗真菌剂的相互作用。还进行了其他试验,如糖醇保护试验、外排泵抑制试验、细胞膜通透性试验和核苷酸泄漏试验。在幼虫中评估了[该药物的]疗效和安全性。阿来西定对[某种真菌]表现出杀菌活性,MIC为0.5μg/mL。生物膜形成受到显著抑制,减少了78.69%。机制研究显示有核苷酸泄漏,表明对膜有影响,但未检测到明显的蛋白质泄漏。此外,阿来西定显示出良好的安全性,在[某种动物]模型中没有溶血或急性毒性的迹象。这些发现支持阿来西定作为抗真菌药物重新利用的有力候选药物,特别是用于治疗[某种真菌]感染。它在抑制生长和生物膜形成方面的疗效,以及良好的安全性,凸显了其作为抗真菌疗法进行临床开发的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/70be/11966325/4bc2ea844685/ao4c11382_0001.jpg

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