Synergistic activity of clioquinol with voriconazole and amphotericin B against fungi of interest in eye infections

IF 2.2 4区 医学 Q3 MYCOLOGY
Paula Reginatto , Giovanna de Jesus Agostinetto , Mário Litieri Teixeira , Saulo Fernandes de Andrade , Alexandre Meneghello Fuentefria
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引用次数: 0

Abstract

Keratoplasty represents a risk factor for fungal eye infections, despites the antibacterial actives in the corneal tissue preservation means, it does not contain active substances with antifungal action. Among the most commonly associated fungal agents are the species belonging to the genera Fusarium and Candida. These agents can trigger an infectious process characterized by swift progression associated with high rates of morbidity, causing irreversible damage. Polyene and azole antifungals are the main agents of ocular therapy, however, they demonstrate some limitations, such as their toxicity and fungal resistance. In this context, drug repositioning and the combination of antifungals may be an alternative. Hence, the goal of this study was to investigate the potential activity of clioquinol (CLQ), a derivative of 8-hydroxyquinoline with previously described antifungal activity, along with its triple and quadruple combinations with antifungal agents commonly used in ophthalmic fungal therapy, natamycin (NAT), voriconazole (VRC), and amphotericin B (AMB), against main fungal pathogens in eye infections. The MICs for CLQ ranged from 0.25 to 2.0 μg/mL, for NAT from 4.0 to 32.0 μg/mL, for AMB it ranged from 0.25 to 16.0 μg/mL and for VRC from 0.03125 to 512.0 µg/mL. Among the tested combinations, the VRC-AMB-CLQ combination stands out, which showed a synergistic effect for more than 50 % of the tested strains and did not present antagonistic results against any of them. Toxicity data were similar to those antifungals already used, even with lower potential toxicity. Therefore, both clioquinol and the triple combination VCR-AMB-CLQ exhibited promising profiles for use as active components in corneal tissue preservation medium.

氯喹酚与伏立康唑和两性霉素 B 对眼部感染真菌的协同作用
角膜塑形术是眼部真菌感染的一个危险因素,尽管角膜组织保存方法中含有抗菌活性物质,但它并不含有具有抗真菌作用的活性物质。最常见的相关真菌包括镰刀菌属和念珠菌属。这些真菌可引发感染过程,其特点是进展迅速,发病率高,造成不可逆转的损害。多烯类和唑类抗真菌药物是眼部治疗的主要药物,但它们也存在一些局限性,如毒性和真菌耐药性。在这种情况下,药物重新定位和联合使用抗真菌药物可能是一种替代方法。因此,本研究的目的是研究具有抗真菌活性的 8-羟基喹啉衍生物氯喹(CLQ)及其与眼科真菌治疗中常用的抗真菌药物纳他霉素(NAT)、伏立康唑(VRC)和两性霉素 B(AMB)的三联和四联疗法对眼部感染中主要真菌病原体的潜在活性。CLQ 的 MIC 值为 0.25-2.0 μg/mL,NAT 为 4.0-32.0 μg/mL,AMB 为 0.25-16.0 μg/mL,VRC 为 0.03125-512.0 µg/mL。在测试的组合物中,VRC-AMB-CLQ 组合物脱颖而出,对 50%以上的受试菌株具有协同增效作用,对任何菌株都没有拮抗作用。毒性数据与已使用的抗真菌药相似,甚至潜在毒性更低。因此,氯喹诺尔和 VCR-AMB-CLQ 三重组合都显示出作为角膜组织保存培养基活性成分的良好前景。
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来源期刊
CiteScore
5.10
自引率
2.80%
发文量
68
审稿时长
6-12 weeks
期刊介绍: The Journal de Mycologie Medicale / Journal of Medical Mycology (JMM) publishes in English works dealing with human and animal mycology. The subjects treated are focused in particular on clinical, diagnostic, epidemiological, immunological, medical, pathological, preventive or therapeutic aspects of mycoses. Also covered are basic aspects linked primarily with morphology (electronic and photonic microscopy), physiology, biochemistry, cellular and molecular biology, immunochemistry, genetics, taxonomy or phylogeny of pathogenic or opportunistic fungi and actinomycetes in humans or animals. Studies of natural products showing inhibitory activity against pathogenic fungi cannot be considered without chemical characterization and identification of the compounds responsible for the inhibitory activity. JMM publishes (guest) editorials, original articles, reviews (and minireviews), case reports, technical notes, letters to the editor and information. Only clinical cases with real originality (new species, new clinical present action, new geographical localization, etc.), and fully documented (identification methods, results, etc.), will be considered. Under no circumstances does the journal guarantee publication before the editorial board makes its final decision. The journal is indexed in the main international databases and is accessible worldwide through the ScienceDirect and ClinicalKey platforms.
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