Seven new polyaromatic bis-spiroketal-containing butenolides, the prunolides D−I (4−9) and cis-prunolide C (10), a new dibrominated β-carboline sulfamate named pityriacitrin C (11), alongside the known prunolides A−C (1−3) were isolated from the Australian colonial ascidian Synoicum prunum. The prunolides D−G (4−7) represent the first asymmetrically brominated prunolides, while cis-prunolide C ( 10) is the first reported with a cis-configuration about the prunolide's bisspiroketal core. The prunolides displayed binding activities with the Parkinson's disease-implicated amyloid protein α-synuclein in a mass spectrometry binding assay, while the prunolides (1−5 and 10) were found to significantly inhibit the aggregation (>89.0%) of α-synuclein in a ThT amyloid dye assay. The prunolides A−C (1−3) were also tested for inhibition of pSyn aggregate formation in a primary embryonic mouse midbrain dopamine neuron model with prunolide B (2) displaying statistically significant inhibitory activity at 0.5 μM. The antiplasmodial and antibacterial activities of the isolates were also examined with prunolide C (3) displaying only weak activity against the 3D7 parasite strain of Plasmodium falciparum. Our findings reported herein suggest that the prunolides could provide a novel scaffold for the exploration of future therapeutics aimed at inhibiting amyloid protein aggregation and the treatment of numerous neurodegenerative diseases.

Three new diterpenes, aplyroseols 20–22 (2–4), were isolated from two specimens of the Australian marine sponge Dendrilla rosea. The structures and relative configurations of the new metabolites were elucidated from analysis of 2D NMR data. The compounds were screened for activity against Staphylococcus aureus, but were inactive at 64µgmL−1.

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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 αsyn aggregation inhibitory structure-activity relationships for this class of compounds.