Synthesis and evaluation of analogues of Congo red as potential compounds against transmissible spongiform encephalopathies.
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.
Rudyk
Hélène
H
Welsh School of Pharmacy, Cardiff University, Redwood Building, King Edward VII Avenue, CF10 3XF Cardiff, UK.
Knaggs
Michael H
MH
Vasiljevic
Snezana
S
Hope
James
J
Birkett
Chris
C
Gilbert
Ian H
IH
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
D000596:Amino Acids; D018621:PrPC Proteins; D003224:Congo Red