含有化海洋衍生氨基酸替代物的抗微生物
Alexander J Craig1,2, Yuri Ermolovich3, Alan Cameron4
1Drug Design and Discovery, Department of Medicinal Chemistry, Biomedical Centre, Uppsala University, 75123 Uppsala, Sweden.
ACS medicinal chemistry letters
|June 14, 2023
概括
合成的阴离子抗微生物显示出治疗持久性感染的前景. 研究人员开发了具有海洋灵感动机的新型三,证明了对低毒性细菌和真菌的强大活性.
科学领域:
- 药用化学 医学化学
- 微生物学 微生物学
- 药物发现 药物发现 药物发现
背景情况:
- 阴离子抗微生物 (CAMP) 在对抗微生物感染方面至关重要.
- 开发具有更高安全性和有效性的合成CAMP模仿剂是一个活跃的研究领域.
- 持续的微生物感染需要新的治疗策略.
研究的目的:
- 合成和评估19种新的线性三作为抗菌剂.
- 通过结合修饰的疏水性氨基酸和阴离子残留物来研究结构-活性关系.
- 评估化合物对病原细菌和真菌的活性,包括临床分离物,并评估它们的安全性.
主要方法:
- 合成了19种线性化三与修饰的疏水性氨基酸和化残留物.
- 对五种致病性细菌和真菌菌株 (包括临床分离物) 进行抗微生物敏感性测试.
- 使用红细胞和HeLa细胞进行体外毒性测定.
主要成果:
- 几种三体表现出高抗微生物活性 (低μM度) 对抗细菌和真菌.
- 与细菌菌株相比,对真菌菌株的活性显著更高.
- 这些化合物在体外对红细胞和HeLa细胞具有低的非标毒性.
结论:
- 设计的合成三体显示出作为抗菌剂的巨大潜力.
- 调节疏水和阴离子元件可以调整活动和选择性.
- 这些化合物代表了开发新治疗方法的前景,用于治疗持久性微生物感染,具有有利的安全性.
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