Cis-Glyco-Fused Benzopyran Derivatives as Hit Compounds for the Development of Therapeutic and Diagnostic Tools against Neurodegenerative Diseases

Authors

  • Dr. Silvia Merlo,

    1. Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milan (Italy), Fax: (+39) 0264483565
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    • These authors contributed equally to this work.

  • Dr. Erika Sironi,

    1. Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milan (Italy), Fax: (+39) 0264483565
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    • These authors contributed equally to this work.

  • Dr. Laura Colombo,

    1. Department of Biochemistry and Molecular Pharmacology, IRCCS–Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa 19, 20156 Milan (Italy)
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  • Dr. Francisco Cardona,

    1. Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milan (Italy), Fax: (+39) 0264483565
    2. Department of Chemistry, University of Aveiro, Campus Universitario de Santiago, 3810-193 Aveiro (Portugal)
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  • Dr. Alessandra M. Martorana,

    1. Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milan (Italy), Fax: (+39) 0264483565
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  • Dr. Mario Salmona,

    1. Department of Biochemistry and Molecular Pharmacology, IRCCS–Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa 19, 20156 Milan (Italy)
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  • Dr. Barbara La Ferla,

    1. Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milan (Italy), Fax: (+39) 0264483565
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  • Dr. Cristina Airoldi

    Corresponding author
    1. Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milan (Italy), Fax: (+39) 0264483565
    • Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milan (Italy), Fax: (+39) 0264483565

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Abstract

Oligomeric and fibrillar aggregates generated by amyloid-β (Aβ) and prion protein (PrP) peptides are amongst the principal components of amyloid plaques found post mortem in patients suffering from Alzheimer’s disease and mammalian prion diseases. Hence these amyloid peptides represent major molecular targets to develop potential drugs and diagnostic tools for the above-mentioned neurodegenerative diseases. Recently, a small library of cis-glyco-fused benzopyran compounds has been synthesized by us, and their ability to recognize and bind Aβ peptide oligomers and stain Aβ deposits was demonstrated. By exploiting the structural similarity between Aβ and PrP aggregates, herein the interaction of these benzopyran molecules with PrP oligomers and their inhibition of the PrP aggregation process that leads to amyloid fibril formation are investigated. Finally, the in vitro staining of PrP fibrils is achieved with a fluorescently labeled cis-glyco-fused benzopyran derivative able to cross a model of the blood–brain barrier.

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