Nature has always played an important role in therapeutics as a provider of bioactive compounds. Specifically, the marine environment is a rich, but underexplored, source of potential bioactive compounds. Recently, there has been an increased interest in marine microorganisms, namely bacteria and fungi, capable of producing secondary metabolites with new scaffolds.

In our efforts to discover compounds with potential to be used as antimicrobial agents and/or adjuvants, we turned our attention to compounds isolated from marine-derived fungi (Aspergillus and Neosartorya genera), presenting different scaffolds, some of which had already shown potential as antibacterial agents. Therefore, the aim of this study was to test nineteen metabolites from marine-derived fungi for their potential as inhibitors of bacterial efflux pumps, one of the most worrisome antimicrobial resistance mechanisms, and of biofilm formation and quorum-sensing, related resistance and virulence mechanisms, .

Results have shown two compounds were effective as Gram-positive efflux pump inhibitors, and three displayed the same activity for the Gram-negative strain tested. Docking studies were useful for molecular visualization of the compounds in the predicted binding sites. Moreover, eight compounds were able to inhibit biofilm formation in the strains tested, and four inhibited quorum-sensing in the models chosen. Cytotoxicity studies were performed in NIH/3T3 cell line, and three compounds could be safely used as antibacterial, efflux pump inhibitors and/or biofilm formation inhibitors.

The outcomes of this study highlight the potential that lies in the sea, and the opportunities for finding new therapies, or inspiration for new molecules.