Synthesis and antimicrobial activity of small cationic amphipathic aminobenzamide marine natural product mimics and evaluation of relevance against clinical isolates including ESBL-CARBA multi-resistant bacteria

Publication date: Available online 20 September 2016
Source:Bioorganic & Medicinal Chemistry
Author(s): Elizaveta M. Igumnova, Ekaterina Mishchenko, Tor Haug, Hans-Matti Blencke, Johanna U. Ericson Sollid, Elizabeth G. Aarag Fredheim, Silje Lauksund, Klara Stensvåg, Morten B. Strøm
A library of small aminobenzamide derivatives was synthesised to explore a cationic amphipathic motif found in marine natural antimicrobials. The most potent compound E23 displayed minimal inhibitory concentrations (MICs) of 0.5 – 2 μg/ml against several Gram-positive bacterial strains, including methicillin resistant Staphylococcus epidermidis (MRSE).E23 was also potent against 275 clinical isolates including Staphylococcus aureus, Enterococcus spp., Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae, as well as methicillin-resistant S. aureus (MRSA), vancomycin-resistant enterococci (VRE), and ESBL-CARBA multi-resistant Gram-negative bacteria. The study demonstrates how structural motifs found in marine natural antimicrobials can be a valuable source for making novel antimicrobial lead-compounds.

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