Synthesis of analogues of Congo red and evaluation of their anti-prion activity

Shane Sellarajah, Tamuna Lekishvili, Claire Bowring, Andrew R. Thompsett, Helene Rudyk, Christopher R. Birkett, David R. Brown, Ian H. Gilbert

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    Abstract

    No cure as of yet exists for any of the transmissible spongiform encephalopathies. In this paper, we describe the synthesis of analogues of Congo red and evaluation against a cellular model of infection, the SMB (scrapie mouse brain) persistently infected cell line, for their ability to inhibit the infectivity of the abnormal form of prion protein (PrP-res). The compounds have also been tested for their ability to inhibit the polymerization of PrPC by PrP-res. A number of analogues showed inhibition of PrP-res infectivity at nanomolar concentrations. Several analogues show promise; the most active compound, 2a, inhibits the formation of PrP-res in SMB cells with an EC50 of 25-50 nM.

    Original languageEnglish
    Pages (from-to)5515-5534
    Number of pages20
    JournalJournal of Medicinal Chemistry
    Volume47
    Issue number22
    DOIs
    Publication statusPublished - 2004

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