Chrysamine-G, a lipophilic analogue of Congo red, inhibits A beta-induced toxicity in PC12 cells.

Increasing evidence suggests that deposition of amyloid-beta (A beta) peptide leads to neurodegeneration in Alzheimer's disease. Congo red, a histologic dye that binds to amyloid has previously been shown to diminish the toxic effects of A beta in cell culture. Since Congo red is too highly charged to enter the brain in significant quantities, a lipophilic derivative, Chrysamine-G, was tested for the ability to attenuate A beta[25-35]-induced toxicity in PC12 cells using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Chrysamine-G showed a concentration-dependent inhibition of A beta[25-35]-induced toxicity. This protective effect became significant at 0.2 microM, a concentration very close to the Ki for Chrysamine-G binding to synthetic A beta (0.37 microM). A decarboxy derivative of Chrysamine-G, which does not bind to A beta, also did not protect against A beta-induced toxicity. The protective effects of Chrysamine-G may relate to its ability to bind directly to A beta and may involve other post-binding effects as well.