6-Bromoindolglyoxylamido derivatives as antimicrobial agents and antibiotic enhancers.
Basic Information
ID: ALA4339208
Journal: Bioorg Med Chem
Title: 6-Bromoindolglyoxylamido derivatives as antimicrobial agents and antibiotic enhancers.
Authors: Li SA, Cadelis MM, Sue K, Blanchet M, Vidal N, Brunel JM, Bourguet-Kondracki ML, Copp BR.
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.
CiteXplore: 30975502
DOI: 10.1016/j.bmc.2019.04.004
Patent ID: ┄