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评估醋酸格拉替雷(Copaxone)作为治疗感染的化疗候选药物的体外潜力。

Assessing the In Vitro Potential of Glatiramer Acetate (Copaxone) as a Chemotherapeutic Candidate for the Treatment of Infection.

作者信息

Alves Vinicius, Martins Pedro Henrique, Miranda Bruna, de Andrade Iara Bastos, Pereira Luiza, Maeda Christina Takiya, de Sousa Araújo Glauber Ribeiro, Frases Susana

机构信息

Laboratório de Biofísica de Fungos, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil.

Laboratório de Fisiopatologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil.

出版信息

J Fungi (Basel). 2023 Jul 25;9(8):783. doi: 10.3390/jof9080783.

Abstract

Cryptococcosis is a systemic mycosis affecting immunosuppressed individuals, caused by various species. The current treatment utilizes a combination of antifungal drugs, but issues such as nephrotoxicity, restricted or limited availability in certain countries, and resistance limit their effectiveness. Repurposing approved drugs presents a viable strategy for developing new antifungal options. This study investigates the potential of glatiramer acetate (Copaxone) as a chemotherapy candidate for infection. Various techniques are employed to evaluate the effects of glatiramer acetate on the fungus, including microdilution, XTT analysis, electron and light microscopy, and physicochemical measurements. The results demonstrate that glatiramer acetate exhibits antifungal properties, with an IC of 0.470 mg/mL and a minimum inhibitory concentration (MIC) of 2.5 mg/mL. Furthermore, it promotes enhanced cell aggregation, facilitates biofilm formation, and increases the secretion of fungal polysaccharides. These findings indicate that glatiramer acetate not only shows an antifungal effect but also modulates the key virulence factor-the polysaccharide capsule. In summary, repurposing glatiramer acetate as a potential chemotherapy option offers new prospects for combating infection. It addresses the limitations associated with current antifungal therapies by providing an alternative treatment approach.

摘要

隐球菌病是一种影响免疫抑制个体的全身性真菌病,由多种菌种引起。目前的治疗方法采用抗真菌药物联合使用,但诸如肾毒性、在某些国家供应受限或有限以及耐药性等问题限制了它们的有效性。重新利用已批准的药物是开发新抗真菌药物的一种可行策略。本研究调查了醋酸格拉替雷(Copaxone)作为感染化疗候选药物的潜力。采用了各种技术来评估醋酸格拉替雷对真菌的影响,包括微量稀释、XTT分析、电子显微镜和光学显微镜以及物理化学测量。结果表明,醋酸格拉替雷具有抗真菌特性,IC为0.470mg/mL,最低抑菌浓度(MIC)为2.5mg/mL。此外,它促进细胞聚集增强,促进生物膜形成,并增加真菌多糖的分泌。这些发现表明,醋酸格拉替雷不仅显示出抗真菌作用,而且还调节关键毒力因子——多糖荚膜。总之,将醋酸格拉替雷重新用作潜在的化疗选择为对抗感染提供了新的前景。它通过提供替代治疗方法解决了与当前抗真菌疗法相关的局限性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/597a/10455304/6964526dcadb/jof-09-00783-g001.jpg

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