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氧化释放动力学对抗真菌活性的影响

Quincy E Grayton¹, Ivie L Conlon¹, Christopher A Broberg¹

¹Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

Journal of fungi (Basel, Switzerland)

|May 24, 2024

概括

氧化 (NO) 具有广泛的抗真菌活性,可以对抗抗性真菌,如Candida和Aspergillus. 具有更快释放动力学的NO供体显示出与现有的抗真菌药物增强的疗效和兼容性.

科学领域:

发现抗微生物药物发现.
菌类学菌类学是指菌类学.
药品化学药品化学是一个

背景情况:

致病性真菌中药物耐药性的增加构成了全球健康的重大挑战.
有限的抗真菌选择和越来越多的抗药性导致医疗保健成本上升,患者的生活质量下降.
氧化 (NO) 已显示出抗菌潜力,但其对真菌病原体的特定影响需要进一步阐明.

研究的目的:

为了研究释放氧化 (NO) 的小分子的广谱抗真菌活性.
评估NO释放动力学对对关键病原菌的抗真菌功效的影响.
评估NO供体与现有抗真菌疗法的兼容性.

主要方法:

对四种释放氧化的小分子进行了测试,对抗 *Candida albicans*, *Candida auris*, *Cryptococcus neoformans* 和 *Aspergillus fumigatus*.
在24小时暴露于一剂量NO的玻尿酸剂后,评估了抗真菌作用.
确定了NO捐赠者半衰期,有效度和选择性指数之间的关系.
检查了处理后的真菌表面形态.
评估了NO供体与常规抗真菌药物的协同作用潜力.

主要成果:

一次剂量NO在24小时内根除了测试的真菌物种.
半衰期较短的NO捐赠者在较低度下表现出强烈的抗真菌活性,表现出更广泛的选择性指数.
所有测试的NO供体都诱导了真菌细胞的显著表面破坏.
所有的NO捐赠体都与目前针对各种真菌物种的处方抗真菌药物相兼容.

结论:

氧化对临床相关的病原菌具有广泛的疗效.
无氧化物捐赠者的受控释放动力学对于优化抗真菌功效和安全至关重要.
释放NO的分子是一个有前途的治疗策略,可能增强现有的抗真菌治疗.

关键词:

亚斯伯吉拉斯烟虫 (Aspergillus fumigatus) 是一种有毒的植物.在Candida albicans中使用.它们是Candida auris.这是Cryptococcus neoformans的新型菌.这是一种抗真菌药物.氧化氧化的使用方法

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