α-Synuclein Aggregation Inhibitory Procerolides and Diphenylalkanes from the Ascidian Polycarpa procera .

The aggregation of the neuronal protein α-synuclein (α-syn) is intrinsically linked to the development and progression of Parkinson's disease (PD). Recently we screened the MeOH extracts from 283 marine invertebrates for α-syn binding activity using an affinity mass spectrometry (MS) binding assay and found that the extract of the ascidian Polycarpa procera displayed activity. A subsequent bioassay-guided purification led to the isolation of one new α-syn aggregation inhibitory butenolide procerolide E ( 3 ) and one new α-syn aggregation inhibitory diphenylbutyrate methyl procerolate A ( 5 ). Herein we report the structure elucidation of procerolide E ( 3 ) and methylprocerolate A ( 5 ) and α-syn aggregation inhibitory activity of procerolides C-E ( 1 - 3 ), methyl procerolate A ( 5 ) and procerone A ( 4 ). We also report the α-syn binding activity of 3-bromo-4-methoxyphenylacetamide ( 6 ) and a synthetic butenolide library, which has allowed us to determine α-syn aggregation inhibitory structure-activity relationships for this class of compounds.