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.
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.
Department of Pharmacy, Faculty of Health Sciences, UiT - The Arctic University of Norway, NO-9037 Tromsø, Norway.
Elizaveta M
EM
Igumnova
The Norwegian College of Fishery Science, Faculty of Biosciences, Fisheries and Economics, UiT - The Arctic University of Norway, NO-9037 Tromsø, Norway.
Ekaterina
E
Mishchenko
The Norwegian College of Fishery Science, Faculty of Biosciences, Fisheries and Economics, UiT - The Arctic University of Norway, NO-9037 Tromsø, Norway.
Tor
T
Haug
The Norwegian College of Fishery Science, Faculty of Biosciences, Fisheries and Economics, UiT - The Arctic University of Norway, NO-9037 Tromsø, Norway.
Hans-Matti
HM
Blencke
Department of Medical Biology, Faculty of Health Sciences, UiT - The Arctic University of Norway, NO-9037 Tromsø, Norway.
Johanna U Ericson
JUE
Sollid
Department of Pharmacy, Faculty of Health Sciences, UiT - The Arctic University of Norway, NO-9037 Tromsø, Norway.
Elizabeth G Aarag
EGA
Fredheim
Department of Pharmacy, Faculty of Health Sciences, UiT - The Arctic University of Norway, NO-9037 Tromsø, Norway.
Silje
S
Lauksund
The Norwegian College of Fishery Science, Faculty of Biosciences, Fisheries and Economics, UiT - The Arctic University of Norway, NO-9037 Tromsø, Norway.
Klara
K
Stensvåg
Department of Pharmacy, Faculty of Health Sciences, UiT - The Arctic University of Norway, NO-9037 Tromsø, Norway.
Morten B
MB
Strøm
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001549:Benzamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001688:Biological Products / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects*; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D001549:Benzamides; D001688:Biological Products
Aminobenzamides; Antibacterial; Antimicrobial; ESBL–CARBA; Marine natural product mimics; Multi-resistant bacteria; Peptidomimetics