Potential of Marine Sponge Metabolites against Prions: Bromotyrosine Derivatives, a Family of Interest.

The screening of 166 extracts from tropical marine organisms (invertebrates, macroalgae) and 3 cyclolipopeptides from microorganisms against yeast prions highlighted the potential of Verongiida sponges to prevent the propagation of prions. We isolated the known compounds purealidin Q ( 1 ), aplysamine-2 ( 2 ), pseudoceratinine A ( 3 ), aerophobin-2 ( 4 ), aplysamine-1 ( 5 ), and pseudoceratinine B ( 6 ) for the first time from the Wallisian sponge Suberea laboutei . We then tested compounds 1 - 6 and sixteen other bromotyrosine and bromophenol derivatives previously isolated from Verongiida sponges against yeast prions, demonstrating the potential of 1 - 3 , 5 , 6 , aplyzanzine C ( 7 ), purealidin A ( 10 ), psammaplysenes D ( 11 ) and F ( 12 ), anomoian F ( 14 ), and N,N-dimethyldibromotyramine ( 15 ). Following biological tests on mammalian cells, we report here the identification of the hitherto unknown ability of the six bromotyrosine derivatives 1 , 2 , 5 , 7 , 11 , and 14 of marine origin to reduce the spread of the PrP ^Sc prion and the ability of compounds 1 and 2 to reduce endoplasmic reticulum stress. These two biological activities of these bromotyrosine derivatives are, to our knowledge, described here for the first time, offering a new therapeutic perspective for patients suffering from prion diseases that are presently untreatable and consequently fatal.
Competing Interests: The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.