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

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

doi:10.1016/j.bmc.2016.09.046

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

Bioorg Med Chem. 2016 Nov 15;24(22):5884-5894. doi: 10.1016/j.bmc.2016.09.046. Epub 2016 Sep 20.

Authors

Elizaveta M Igumnova¹, Ekaterina Mishchenko², Tor Haug², Hans-Matti Blencke², Johanna U Ericson Sollid³, Elizabeth G Aarag Fredheim¹, Silje Lauksund¹, Klara Stensvåg², Morten B Strøm¹

Affiliations

¹ Department of Pharmacy, Faculty of Health Sciences, UiT - The Arctic University of Norway, NO-9037 Tromsø, Norway.
² The Norwegian College of Fishery Science, Faculty of Biosciences, Fisheries and Economics, UiT - The Arctic University of Norway, NO-9037 Tromsø, Norway.
³ Department of Medical Biology, Faculty of Health Sciences, UiT - The Arctic University of Norway, NO-9037 Tromsø, Norway.

PMID: 27692769
DOI: 10.1016/j.bmc.2016.09.046

Abstract

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 0.5-2μg/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 producing 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.

Keywords: Aminobenzamides; Antibacterial; Antimicrobial; ESBL–CARBA; Marine natural product mimics; Multi-resistant bacteria; Peptidomimetics.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Bacterial Agents / chemical synthesis
Anti-Bacterial Agents / chemistry
Anti-Bacterial Agents / pharmacology*
Antimicrobial Cationic Peptides / chemical synthesis
Antimicrobial Cationic Peptides / chemistry
Antimicrobial Cationic Peptides / pharmacology*
Benzamides / chemical synthesis
Benzamides / chemistry
Benzamides / pharmacology*
Biological Products / chemical synthesis
Biological Products / chemistry
Biological Products / pharmacology*
Dose-Response Relationship, Drug
Drug Resistance, Multiple, Bacterial / drug effects*
Gram-Negative Bacteria / drug effects
Gram-Positive Bacteria / drug effects
Microbial Sensitivity Tests
Molecular Structure
Structure-Activity Relationship

Substances

Anti-Bacterial Agents
Antimicrobial Cationic Peptides
Benzamides
Biological Products