简单的两性胆汁酸功能化抗菌剂:对抗致病细菌,真菌及其生物膜
Swagatam Barman1,2, Leman Buzoglu Kurnaz1, Xiaoming Yang3
1Department of Chemistry and Biochemistry, University of South Carolina, Columbia, South Carolina 29208, United States.
ACS infectious diseases
|August 3, 2023
概括
新的基于胆酸的抗微生物药物显示出对细菌和真菌的广泛活性. 这些化合物有效地消除生物膜和休眠细胞,而不会诱导耐药性,为传统抗生素提供了有希望的替代品.
科学领域:
- 药用化学 医学化学
- 抗菌研究 抗菌研究
- 生物化学 生物化学
背景情况:
- 传统的抗生素面临的挑战是对休眠的细菌群体和生物膜的耐药性和有效性.
- 开发具有广谱活性和降低毒性的新型抗菌剂是一个至关重要的未满足需求.
- 胆汁酸,天然的两性分子,为抗菌药物发现提供了一个尚未探索的支架.
研究的目的:
- 合成和评估基于胆酸的新型双胞胎胆酸化合物作为抗菌剂.
- 评估这些化合物对一系列细菌和真菌病原体的疗效,包括生物膜和休眠细胞.
- 调查作用机制和抗药性发展的潜力.
主要方法:
- facially 两性胆酸衍生物的合成.
- 对各种细菌和真菌菌株进行抗微生物敏感性测试.
- 生物膜根除和抑制测定.
- 对哺乳动物细胞的细胞毒性评估.
- 涉及膜相互作用和反应性氧物种 (ROS) 生成的机制研究.
- 细菌耐药性发展的测试.
主要成果:
- 合成的基于胆汁酸的化合物表现出广泛的抗微生物活性,对抗阳性细菌,阴性细菌和真菌.
- 两种化合物显示出强大的消灭休眠细菌亚群,并建立了MRSA,P. aeruginosa和C. albicans的生物膜.
- 这些化合物对哺乳动物细胞具有微不足道的毒性.
- 机理学研究表明,膜破坏和内源性ROS的诱导是关键的抗菌作用.
- 在长时间暴露后,在细菌菌株中没有观察到可检测的耐药性.
结论:
- 基于容易两性胆酸的抗微生物药物代表了一种有前途的新型治疗药物.
- 这些化合物比传统抗生素具有优势,包括对生物膜,休眠细胞的有效性,以及对抗药性发展的低倾向.
- 膜向机制和ROS诱导提供了一种独特的方法来对抗微生物感染.
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