School of Chemistry, Raymond and Beverly Sackler Faculty of Exact Sciences, Tel Aviv University, Tel Aviv, 6997801 (Israel).
Angew Chem Int Ed Engl. 2015 Nov 9;54(46):13617-21. doi: 10.1002/anie.201506814. Epub 2015 Sep 29.
The effect of di-N-methylation of bacterial membrane disruptors derived from aminoglycosides (AGs) on antimicrobial activity is reported. Di-N-methylation of cationic amphiphiles derived from several diversely structured AGs resulted in a significant increase in hydrophobicity compared to the parent compounds that improved their interactions with membrane lipids. The modification led to an enhancement in antibacterial activity and a broader antimicrobial spectrum. While the parent compounds were either modestly active or inactive against Gram-negative pathogens, the corresponding di-N-methylated compounds were potent against the tested Gram-negative as well as Gram-positive bacterial strains. The reported modification offers a robust strategy for the development of broad-spectrum membrane-disrupting antibiotics for topical use.
报道了氨基糖苷类（AGs）衍生的细菌膜破坏剂的二-N-甲基化对其抗菌活性的影响。与母体化合物相比，几种结构各异的 AG 衍生的阳离子两亲物的二-N-甲基化导致疏水性显著增加，从而改善了它们与膜脂的相互作用。修饰导致抗菌活性增强和抗菌谱扩大。虽然母体化合物对革兰氏阴性病原体的活性适中或无活性，但相应的二-N-甲基化化合物对测试的革兰氏阴性和革兰氏阳性细菌菌株均具有很强的活性。所报道的修饰为开发用于局部应用的广谱膜破坏抗生素提供了一种强大的策略。
