2. Academic Validation
  3. Exploration of the antibiotic potentiating activity of indolglyoxylpolyamines

Exploration of the antibiotic potentiating activity of indolglyoxylpolyamines

  • Eur J Med Chem. 2019 Dec 1:183:111708. doi: 10.1016/j.ejmech.2019.111708.
Melissa M Cadelis 1,  Elliot I W Pike 1,  Weirong Kang 2,  Zimei Wu 2,  Marie-Lise Bourguet-Kondracki 3,  Marine Blanchet 4,  Nicolas Vidal 5,  Jean Michel Brunel 4,  Brent R Copp 6
Affiliations

Affiliations

  • 1 School of Chemical Sciences, The University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand.
  • 2 School of Pharmacy, The University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand.
  • 3 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.
  • 4 Aix Marseille Univ, INSERM, SSA, MCT, Faculté de Pharmacie, 27 bd Jean Moulin, 13385, Marseille, France.
  • 5 YELEN, 10 bd Tempête, 13820, Ensues la Redonne, France.
  • 6 School of Chemical Sciences, The University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand. Electronic address: b.copp@auckland.ac.nz.
PMID: 31550659 DOI: 10.1016/j.ejmech.2019.111708
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.

Keywords

Antimicrobial; Indole; Indolglyoxylamide; Polyamine; Potentiation.

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