探索双米多聚胺作为内在的抗菌剂和抗生素增强剂
Melissa M Cadelis1,2, Jisoo Kim2, Florent Rouvier3
1Department of Molecular Medicine and Pathology, School of Medical Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand.
Biomolecules
|July 29, 2023
概括
像ianthelliformisamine C这样的海洋化合物在对抗细菌方面表现有前途. 合成的类似物显示,非化,链较长的化合物是增强抗生素对Pseudomonas aeruginosa的作用最好的.
科学领域:
- 海洋天然产品化学 海洋天然产品化学
- 药品化学 药品化学 是一个
- 发现抗微生物药物发现.
背景情况:
- Ianthelliformisamine C是一种海洋天然产品,是一种具有抗菌活性的bis-cinnamido精氨酸衍生物.
- 它增强了多西环素对格拉姆阴性细菌Pseudomonas aeruginosa的疗效.
- 其类型的结构-活性关系 (SAR) 对于优化抗微生物和抗生素增强性质至关重要.
研究的目的:
- 合成和评估甲胺C的类似物.
- 研究甲基,原子和聚胺链长度对抗微生物活性和抗生素增强的影响.
- 确定具有潜在的非有毒类型,作为抗微生物疗法的化合物.
主要方法:
- 一个多样化的ianthelliformisamine C类似物库的合成.
- 对黄金葡萄球菌 (Staphylococcus aureus),MRSA,新型菌 (Cryptococcus neoformans),新型菌 (Pseudomonas aeruginosa) 和大肠杆菌 (Escherichia coli) 的抗菌感受性测试.
- 细胞毒性和红细胞血解分析.
- 确定多克西环林增强活性.
主要成果:
- 带有较长聚胺链的非化类型显示出对格拉姆阳性细菌和真菌的抗菌活性.
- 类类似物对阳性和阴性细菌都表现出活性.
- 观察到对格拉姆阴性细菌的活性较弱,除了针对大肠杆菌的特定长链类型外.
- 几种类似物显示出细胞毒性和溶血性质.
- 非有毒的非类同类13b和13d显著增强了多克西环素对P. aeruginosa的活性 (分别是64倍和32倍).
结论:
- 抗微生物和抗生素增强活性受到芳香环替代剂和聚胺链长度的影响.
- 具有较长聚胺链的非化,非甲基化类型具有优化增强抗生素性能的潜力.
- 未来的研究应该专注于各种芳香替代剂,不包括和甲基,以开发有效的米多聚胺基疗法.
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