title: Synthesis and evaluation of analogues of Congo red as potential compounds against transmissible spongiform encephalopathies.
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.
authors.affiliation: Welsh School of Pharmacy, Cardiff University, Redwood Building, King Edward VII Avenue, CF10 3XF Cardiff, UK.
authors.forename: Hélène
authors.initials: H
authors.lastname: Rudyk
authors.forename: Michael H
authors.initials: MH
authors.lastname: Knaggs
authors.forename: Snezana
authors.initials: S
authors.lastname: Vasiljevic
authors.forename: James
authors.initials: J
authors.lastname: Hope
authors.forename: Chris
authors.initials: C
authors.lastname: Birkett
authors.forename: Ian H
authors.initials: IH
authors.lastname: Gilbert
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D003224:Congo Red / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D009010:Monte Carlo Method; D018621:PrPC Proteins / Q000378:metabolism*; D017096:Prion Diseases / Q000188:drug therapy; D012756:Sheep
chemical_list: D000596:Amino Acids; D018621:PrPC Proteins; D003224:Congo Red