| Autor: |
Darren C. Holland, Dale W. Prebble, Safak Er, Joshua B. Hayton, Luke P. Robertson, Vicky M. Avery, Andrii Domanskyi, Milton J. Kiefel, John N. A. Hooper, Anthony R. Carroll |
| Přispěvatelé: |
Division of Pharmacology and Pharmacotherapy, Institute of Biotechnology, Helsinki Institute of Life Science HiLIFE, Biosciences |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
|
| Popis: |
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 bis-spiroketal 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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
