6-Bromoindolglyoxylamido derivatives as antimicrobial agents and antibiotic enhancers

Steven A Li (1) , Melissa Cadelis (1) , Kenneth Sue (1) , Marine Blanchet (2) , Nicolas Vidal (3) , Jean Michel Brunel (2) , Marie-Lise Bourguet-Kondracki (4) , Brent Copp (1)

1 School of Chemical Sciences [Auckland]
2 MCT - Membranes et cibles thérapeutiques
3 YELEN
4 MCAM - Molécules de Communication et Adaptation des Micro-organismes

Dedication In memory of Dr. Jiayi (Jane) Wang. 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 that exhibited intrinsic antimicrobial activity towards Gram-positive bacteria, Staphylococcus aureus and S. intermedius with one of the compounds also displaying in vitro antibiotic enhancing properties against the resistant Gram-negative bacterium Pseudomonas aeruginosa. A series of 6-bromo derivatives were prepared and biologically evaluated, identifying analogues with enhanced antibacterial activity towards Escherichia coli and with moderate to excellent antifungal properties. The mechanism of action of one of the compounds was attributed to rapid membrane permeabilisation and depolarisation in both Gram-positive and Gram-negative bacteria.

Keywords: Antibiotics; antimicrobial; bromoindole; polyamine; potentiation

Domains: Chemical Sciences; Chemical Sciences; Organic chemistry; Life Sciences [q-bio]; Life Sciences [q-bio]; Microbiology and Parasitology; Life Sciences [q-bio]; Microbiology and Parasitology; Bacteriology

Steven A Li, Melissa Cadelis, Kenneth Sue, Marine Blanchet, Nicolas Vidal, et al.. 6-Bromoindolglyoxylamido derivatives as antimicrobial agents and antibiotic enhancers. Bioorganic and Medicinal Chemistry, 2019, 27 (10), pp.2090-2099. ⟨hal-02392399⟩