P46 Antibacterial Marine Natural Product Mimics for treatment of infections

P46 Antibacterial Marine Natural Product Mimics for treatment of infections

Ekaterina Mishchenko1, Elizaveta Igumnova2, Johanna Sollid3, Hans-Matti Blencke1, Silje Lauksund1, Tor Haug1, Elizabeth Fredheim4, Morten Strøm2 and Klara Stensvåg1

1The Norwegian College Of Fishery Science, Uit-The Arctic University Of Norway, Tromsø, NOR 2Department Of Pharmacy, Uit-The Arctic University Of Norway, Tromsø, NOR

3Department Of Medical Biology, Uit-The Arctic University Of Norway, Tromsø, NOR
4Department Of Clinical Medicine, Uit-The Arctic University Of Norway, Tromsø, NOR

In spite of today’s technological progress, ordinary bacterial infections are still among the urgent global challenges. Constant emergence of bacteria resistant to conventional antibiotics, combined with the deficiency of antimicrobial drugs in development reveals the need for novel solutions, such as compounds with novel/unique structures and properties.

A library of small compounds, based on known marine natural antimicrobials and constructed using the bioactivity-guided synthesis approach, was characterized. Bioactivity-screening platform included laboratory reference bacterial panel and expanded panels of clinical isolates of human pathogenic bacteria, including drug-resistant bacteria. Compound E23 was among several promising molecules, especially active against Gram-positive bacteria.

Panel of in vitro assays with model bacterial strains was used to characterize the mode of action of E23. Thus, cytoplasmic membrane depolarization and disruption was shown to be the primary killing mechanism of E23. Resistance development in bacteria towards E23 was not revealed by serial passage experiment.