期刊
JOURNAL OF NATURAL PRODUCTS
卷 85, 期 2, 页码 441-452出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.jnatprod.1c01172
关键词
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资金
- Academy of Finland [293392, 319195]
- University of Helsinki Doctoral Program on Drug Research
- Australian Postgraduate Award (APA) by the Australian Commonwealth Government
- Academy of Finland (AKA) [293392, 319195, 293392, 319195] Funding Source: Academy of Finland (AKA)
Seven new compounds were isolated from an Australian marine organism and further studied. These compounds may have potential for treating protein aggregation issues in neurodegenerative diseases.
Seven new polyaromatic bis-spiroketal-containing butenolides, the prunolides D-I (4-9) and cis-prunolide C (10), a new dibrominated beta-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 bis-spiroketal core. The prunolides displayed binding activities with the Parkinson's disease-implicated amyloid protein alpha-synuclein in a mass spectrometry binding assay, while the prunolides (1-5 and 10) were found to significantly inhibit the aggregation (>89.0%) of alpha-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 mu M. 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.
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