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.

In a study aimed at identifying new anti-prion compounds we screened a library of 500 Australian marine invertebrate derived extracts using a yeast-based anti-prion assay. This resulted in an extract from the subtropical sponge Lamellodysidea cf. chlorea showing potent anti-prion activity. The bioassay-guided investigation of the sponge extract led to the isolation of three new bioactive polyoxygenated steroids, lamellosterols A−C (1−3). These sterols were all isolated in low yield, and their structures elucidated by extensive NMR and MS data analysis. Lamellosterols A−C displayed potent anti-prion activity against the [PSI + ] yeast prion (EC 50 s of 12.7, 13.8, and 9.8 μM, respectively). Lamellosterol A (1) was further shown to bind to the Parkinson's disease implicated amyloid protein, α-synuclein, and to significantly inhibit its aggregation. Our findings indicate that these polyoxygenated sterol sulfates may be useful compounds to study mechanisms associated with neurodegenerative diseases.

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Citronamine A (1), an isoquinoline alkaloid containing an unprecedented pentacyclic ring system, was isolated from the Australian marine sponge Citronia astra. Based on the combination of MS and NMR analyses and comparison of experimental and TDDFT calculated ECD spectra, the absolute structure of 1 was determined. Compound 1 displayed moderate activity against drug sensitive (3D7) and drug resistant (Dd2) strains of the parasite, Plasmodium falciparum, responsible for malaria.