Abstract
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.
Original language | English |
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Pages (from-to) | 13617-13621 |
Number of pages | 5 |
Journal | Angewandte Chemie - International Edition |
Volume | 54 |
Issue number | 46 |
DOIs | |
State | Published - 1 Nov 2015 |
Externally published | Yes |
Bibliographical note
Publisher Copyright:© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Keywords
- aminoglycosides
- antibiotics
- bacteria
- cationic amphiphiles
- membrane disruption