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Di‐ N ‐Methylation of Anti‐Gram‐Positive Aminoglycoside‐Derived Membrane Disruptors Improves Antimicrobial Potency and Broadens Spectrum to Gram‐Negative Bacteria
Author(s) -
Benhamou Raphael I.,
Shaul Pazit,
Herzog Ido M.,
Fridman Micha
Publication year - 2015
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201506814
Subject(s) - antimicrobial , gram , aminoglycoside , methylation , gram negative bacteria , chemistry , bacteria , gram positive bacteria , membrane , antibiotics , antibacterial activity , microbiology and biotechnology , biochemistry , biology , escherichia coli , organic chemistry , dna , gene , genetics
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.