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  • Anti-prion and α-Synuclein Aggregation Inhibitory Sterols from the Sponge Lamellodysidea cf. chlorea

    Author(s)
    Jennings, Laurence K
    Prebble, Dale W
    Xu, Mingming
    Ekins, Merrick G
    Munn, Alan L
    Mellick, George D
    Carroll, Anthony R
    Griffith University Author(s)
    Munn, Alan L.
    Carroll, Anthony R.
    Mellick, George
    Year published
    2020
    Metadata
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    Abstract
    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+] ...
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    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 (EC50s 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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    Journal Title
    Journal of Natural Products
    DOI
    https://doi.org/10.1021/acs.jnatprod.0c01168
    Note
    This publication has been entered as an advanced online version in Griffith Research Online.
    Subject
    Chemical sciences
    Biological sciences
    Biomedical and clinical sciences
    Publication URI
    http://hdl.handle.net/10072/399996
    Collection
    • Journal articles

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