Exploration of the antibiotic potentiating activity of indolglyoxylpolyamines

Melissa M. Cadelis, Elliot I.W. Pike, Weirong Kang, Zimei Wu, Marie Lise Bourguet-Kondracki, Marine Blanchet, Nicolas Vidal, Jean Michel Brunel, Brent R. Copp*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

A series of substituted di-indolglyoxylamido-spermine analogues were prepared and evaluated for intrinsic antimicrobial properties and the ability to enhance antibiotic action. As a compound class, intrinsic activity was typically observed towards Gram-positive bacteria and the fungus Cryptococcus neoformans, with notable exceptions being the 5-bromo- and 6-chloro-indole analogues which also exhibited modest activity (MIC 34–50 μM) towards the Gram-negative bacteria Escherichia coli and Klebsiella pneumoniae. Several analogues enhanced the activity of doxycycline towards the Gram-negative bacteria Pseudomonas aeruginosa, E. coli, K. pneumoniae and Acinetobacter baumannii. Of particular note was the identification of five antibiotic enhancing analogues (5-Br, 7-F, 5-Me, 7-Me, 7-OMe) which also exhibited low to no cytotoxicity and red blood cell haemolytic properties. The mechanisms of action of the 5-Br and 7-F analogues were attributed to the ability to disrupt the integrity of, and depolarize, bacterial membranes.

Original languageEnglish
Article number111708
JournalEuropean Journal of Medicinal Chemistry
Volume183
DOIs
Publication statusPublished - 1 Dec 2019
Externally publishedYes

Scopus Subject Areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

User-Defined Keywords

  • Polyamine
  • Indole
  • Indolglyoxylamide
  • Potentiation
  • Antimicrobial

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