α-Synuclein binding activity of the plant growth promoter asterubine

Dale W Prebble; Safak Er; Irena Hlushchuk; Andrii Domanskyi; Mikko Airavaara; Merrick G Ekins; George D Mellick; Anthony R Carroll

doi:10.1016/j.bmcl.2022.128677

α-Synuclein binding activity of the plant growth promoter asterubine

Bioorg Med Chem Lett. 2022 May 15:64:128677. doi: 10.1016/j.bmcl.2022.128677. Epub 2022 Mar 14.

Authors

Dale W Prebble¹, Safak Er², Irena Hlushchuk³, Andrii Domanskyi⁴, Mikko Airavaara⁵, Merrick G Ekins⁶, George D Mellick¹, Anthony R Carroll⁷

Affiliations

¹ School of Environment and Science, Griffith University (Gold Coast Campus), Parklands Drive, Southport, QLD 4222, Australia; Griffith Institute for Drug Discovery, Griffith University (Brisbane Innovation Park), Don Young Road, Nathan, QLD 4111, Australia.
² Faculty of Pharmacy, University of Helsinki, Helsinki 00014, Finland; Institute of Biotechnology, HiLIFE, University of Helsinki, Helsinki 00014, Finland.
³ Faculty of Pharmacy, University of Helsinki, Helsinki 00014, Finland.
⁴ Institute of Biotechnology, HiLIFE, University of Helsinki, Helsinki 00014, Finland.
⁵ Faculty of Pharmacy, University of Helsinki, Helsinki 00014, Finland; Neuroscience Center, HiLIFE, University of Helsinki, Helsinki 00014, Finland.
⁶ Griffith Institute for Drug Discovery, Griffith University (Brisbane Innovation Park), Don Young Road, Nathan, QLD 4111, Australia; Queensland Museum, South Brisbane BC, QLD 4101, Australia.
⁷ School of Environment and Science, Griffith University (Gold Coast Campus), Parklands Drive, Southport, QLD 4222, Australia; Griffith Institute for Drug Discovery, Griffith University (Brisbane Innovation Park), Don Young Road, Nathan, QLD 4111, Australia. Electronic address: a.carroll@griffith.edu.au.

PMID: 35301136
DOI: 10.1016/j.bmcl.2022.128677

Abstract

Preventing the aggregation of certain amyloid proteins has the potential to slow down the progression of diseases like Alzheimer's, Parkinson's, and type 2 diabetes mellitus. During a high-throughput screen of 300 Australian marine invertebrate extracts, the extract of the marine sponge Thorectandra sp. 4408 displayed binding activity to the Parkinson's disease-associated protein, α-synuclein. Isolation of the active component led to its identification as the known plant growth promoter asterubine (1). This molecule shares distinct structural similarities with potent amyloid beta aggregation inhibitors tramiprosate (homotaurine) and ALZ-801. Herein we report the isolation, NMR data acquired in DMSO and α-synuclein binding activity of asterubine (1).

Keywords: Alkaloid; Alpha synuclein; Amyloid aggregation; Parkinon's disease; Sponges.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amyloid / metabolism
Amyloid beta-Peptides / metabolism
Australia
Diabetes Mellitus, Type 2*
Humans
Parkinson Disease* / metabolism
alpha-Synuclein

Substances

Amyloid
Amyloid beta-Peptides
alpha-Synuclein