α-synuclein aggregation inhibitory activity of the bromotyrosine derivatives aerothionin and aerophobin-2 from the subtropical marine sponge Aplysinella sp

The neuronal protein α-synuclein (α-syn) is one of the main constituents intracellular amyloid aggregations found in post-mortem brains Parkinson’s disease (PD) patients. Recently, we screened MEOH extracts obtained from 300 sub-tropical marine invertebrates for α-syn binding activity using affinity MS and this resulted extract Verongida sponge Aplysinella sp. 1194, (QM G339263) displaying molecules that bind to protein. subsequent bioassay-guided separation led isolation known bromotyrosine derivatives (+)-aerothionin (1) (+)-aerophobin-2 (2). Both compounds as detected by a assay inhibit aggregation an uses fluorescence probe, thioflavin T, detect aggregation. (+)-Aerothionin was toxic primary dopaminergic neurons at its expected inhibitory concentration so could not be tested pSyn aggregates functional assay. (+)-Aerophobin-2 (2) shown weakly 10 µM.