Di-alkylated paromomycin derivatives: Targeting the membranes of Gram positive pathogens that cause skin infections

Yifat Berkov-Zrihen, Ido M. Herzog, Mark Feldman, Adar Sonn-Segev, Yael Roichman, Micha Fridman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

A collection of paromomycin-based di-alkylated cationic amphiphiles differing in the lengths of their aliphatic chain residues were designed, synthesized, and evaluated against 14 Gram positive pathogens that are known to cause skin infections. Paromomycin derivatives that were di-alkylated with C7 and C8 linear aliphatic chains had improved antimicrobial activities relative to the parent aminoglycoside as well as to the clinically used membrane-targeting antibiotic gramicidin D; several novel derivatives were at least 16-fold more potent than the parent aminoglycoside paromomycin. Comparison between a di-alkylated and a mono-alkylated paromomycin indicated that the di-alkylation strategy leads to both an improvement in antimicrobial activity and to a dramatic reduction in undesired red blood cell hemolysis caused by many aminoglycoside-based cationic amphiphiles. Scanning electron microscopy provided evidence for cell surface damage by the reported di-alkylated paromomycins.

Original languageEnglish
Pages (from-to)3624-3631
Number of pages8
JournalBioorganic and Medicinal Chemistry
Volume21
Issue number12
DOIs
StatePublished - 15 Jun 2013

Keywords

  • Amphiphilic aminoglycosides
  • Cationic amphiphiles
  • Hemolysis
  • Membrane-targeting antibiotics
  • Skin infection causing bacteria

Fingerprint

Dive into the research topics of 'Di-alkylated paromomycin derivatives: Targeting the membranes of Gram positive pathogens that cause skin infections'. Together they form a unique fingerprint.

Cite this