NR ARKB
AU Sellarajah,S.; Lekishvili,T.; Bowring,C.; Thompsett,A.R.; Rudyk,H.; Birkett,C.R.; Brown,D.R.; Gilbert,I.H.
TI Synthesis of analogues of Congo red and evaluation of their anti-prion activity
QU Journal of Medicinal Chemistry 2004 Oct 21; 47(22): 5515-34
PT journal article
AB 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 (PrPres). The compounds have also been tested for their ability to inhibit the polymerization of PrPc by PrPres. A number of analogues showed inhibition of PrPres infectivity at nanomolar concentrations. Several analogues show promise; the most active compound, 2a, inhibits the formation of PrPres in SMB cells with an EC50 of 25-50 nM.
MH Animals; Benzamides/*chemical synthesis/pharmacology; Biopolymers; Brain/pathology; Cell Line; Congo Red/*analogs & derivatives/*chemical synthesis/pharmacology; Hydroxybenzoic Acids/*chemical synthesis/pharmacology; Inhibitory Concentration 50; Mice; PrPc Proteins/chemistry; PrPsc Proteins/chemistry; Prions/*antagonists & inhibitors/biosynthesis; Research Support, Non-U.S. Gov't; Scrapie/pathology; Structure-Activity Relationship; Toxicity Tests
AD Welsh School of Pharmacy, Cardiff University, King Edward VII Avenue, Cardiff CF10 3XF, UK
SP englisch
PO USA