赞的合成衍生物具有高的抗甘地胺活性和积极的菌性选择性指数值
Kamila Rząd1, Rachel Ioannidi2, Panagiotis Marakos2
1Department of Pharmaceutical Technology and Biochemistry, Faculty of Chemistry and BioTechMed Center, Gdańsk University of Technology, 11/12 Narutowicza Str., 80-233, Gdańsk, Poland.
Scientific reports
|July 23, 2023
概括
新的合成香素显示出强大的抗真菌活性对抗耐药性Candida albicans. 这些化合物通过向毒酶II来杀死真菌,为现有治疗提供了一个有希望的替代方案.
科学领域:
- 药用化学 医学化学
- 菌类学 菌类学是指菌类学.
- 抗微生物耐药性 抗微生物耐药性
背景情况:
- 抗微生物耐药性和真菌感染的增加,特别是在COVID-19患者中,需要新的抗真菌剂.
- 克桑是一种具有潜在抗真菌性能的化合物,但它们的作用机制往往不太清楚.
研究的目的:
- 为了合成和评估抗真菌活性的新型桑衍生物.
- 阐明强效的桑衍生物对抗白 Candida 的作用机制.
主要方法:
- 新型桑衍生物的合成.
- 针对基准和抗可纳抗性的Candida albicans菌株进行抗真菌活性测试.
- 对化合物与真菌排泄 (ABC输送器和Mdr1p) 相互作用的评估.
- 对人类细胞系的细胞毒性评估和选择性指数的确定.
- 研究对酵母豆酶II活性的影响.
主要成果:
- 合成的尚衍生物44显示出强烈的抗真菌活性,对敏感和耐药的Candida albicans有很强的抗真菌活性.
- 化合物42和44不是主要真菌排泄 (Cdr1p,Cdr2p,Mdr1p) 的基板,这表明它们逃避常见的抵抗机制.
- 这些化合物表现出杀菌作用模式,降低了耐药性发展的风险.
- 新型尚对人体细胞具有中度的细胞毒性,对病原性真菌具有有利的选择性指数.
- 化合物42和44被确定为酵母毒素酶II的抑制剂.
结论:
- 新型的合成香,特别是衍生品42和44,具有显著的抗真菌潜力,可以对抗耐药的Candida albicans.
- 它们的杀菌机制准topoisomerase II,缺乏排泄基底的识别,突显了它们在打击抗真菌耐药性的承诺.
- 作为一种类型的抗真菌药物,进一步研究香素是有必要的.
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