Synthesis and evaluation of analogues of congo red as potential compounds against transmissible spongiform. encephalopathies

Hélène Rudyk, Michael H. Knaggs, Snezana Vasiljevic, James Hope, Chris Birkett, Ian H. Gilbert

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    Abstract

    The synthesis of analogues of the amyloid stain Congo red (1) as potential compounds against transmissible spongiform encephalopathies (TSEs) is reported. Using the direct method, aniline (2) or diamines such as 4,4'-diaminodiphenylsulfone (dapsone, 9), 3,3'-diaminodiphenylsulfone (10), benzidine (11), 3,3-dimethoxybenzidine (12) or 3,3-dichlorobenzidine (13) were diazotised to afford the corresponding diazonium, salts, which without isolation, were directly used for coupling with a range of aromatic sulfonic or carboxylic acids to provide the corresponding truncated dyes analogues of Congo red, 4, 6, 8, and the symmetrical bis azoic dyes 14-19, 21-22, 24 and 26-29 as their sodium salts. Compounds were assayed in a cellular model of scrapie, a sheep TSE. Some of the compounds were shown to have similar activity to the lead compound Congo red. Molecular modelling was carried out to investigate potential structure-activity relationships (SARs) relating to the size and shape of Congo Red analogues. Within the range of compounds tested no discernible SARs were found. (C) 2003 Editions scientifiques et medicales Elsevier SAS. All rights reserved.

    Original languageEnglish
    Pages (from-to)567-579
    Number of pages13
    JournalEuropean Journal of Medicinal Chemistry
    Volume38
    Issue number6
    DOIs
    Publication statusPublished - 2003

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