2. Academic Validation
  3. 6-Bromoindolglyoxylamido derivatives as antimicrobial agents and antibiotic enhancers

6-Bromoindolglyoxylamido derivatives as antimicrobial agents and antibiotic enhancers

  • Bioorg Med Chem. 2019 May 15;27(10):2090-2099. doi: 10.1016/j.bmc.2019.04.004.
Steven A Li 1,  Melissa M Cadelis 1,  Kenneth Sue 1,  Marine Blanchet 2,  Nicolas Vidal 3,  Jean Michel Brunel 2,  Marie-Lise Bourguet-Kondracki 4,  Brent R Copp 5
Affiliations

Affiliations

  • 1 School of Chemical Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand.
  • 2 Aix Marseille Univ, INSERM, SSA, MCT, Faculté de pharmacie, 27 bd Jean Moulin, 13385 Marseille, France.
  • 3 YELEN, 10 bd Tempête, 13820 Ensues la Redonne, France.
  • 4 Laboratoire Molécules de Communication et Adaptation des Micro-organismes, UMR 7245 CNRS, Muséum National d'Histoire Naturelle, 57 rue Cuvier (C.P. 54), 75005 Paris, France.
  • 5 School of Chemical Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand. Electronic address: b.copp@auckland.ac.nz.
PMID: 30975502 DOI: 10.1016/j.bmc.2019.04.004
Abstract

The combination of increased incidence of drug-resistant strains of bacteria and a lack of novel drugs in development creates an urgency for the search for new antimicrobials. Initial screening of compounds from an in-house library identified two 6-bromoindolglyoxylamide polyamine derivatives (3 and 4) that exhibited intrinsic antimicrobial activity towards Gram-positive bacteria, Staphylococcus aureus and S. intermedius with polyamine 3 also displaying in vitro Antibiotic enhancing properties against the resistant Gram-negative bacterium Pseudomonas aeruginosa. A series of 6-bromo derivatives (5-15) were prepared and biologically evaluated, identifying analogues with enhanced Antibacterial activity towards Escherichia coli and with moderate to excellent Antifungal properties. Polyamine 3, which includes a spermine chain, was the most potent of the series - its mechanism of action was attributed to rapid membrane permeabilization and depolarization in both Gram-positive and Gram-negative bacteria.

Keywords

Antibiotics; Antimicrobial; Bromoindole; Polyamine; Potentiation.

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