Chelating Compound, Chrysoidine, Is More Effective in Both Antiprion Activity and Brain Endothelial Permeability Than Quinacrine
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1. As an extension of our previous study of quinacrine and its derivatives, chelating chemicals were screened to obtain more effective, better brain-permeable antiprion compounds using either prion-infected neuroblastoma cells or brain capillary endothelial cells.
2. Eleven chemicals were found to have antiprion activity. Most of them shared a common structure consisting of benzene or naphthalene at either end of an azo bond. Structure–activity data suggest that chelating activity is not necessary but might contribute to the antiprion action.
3. Chrysoidine, a representative compound found here, was about 27 times more effective in the antiprion activity and five times more efficiently permeable through the brain capillary endothelial cells than quinacrine was.
4. These chemicals might be useful as compounds for development of therapeutics for prion diseases.
KEY WORDSprion chrysoidine blood–brain barrier aromatic azo compounds therapy chelating agents brain endothelial cells prion-infected neuroblastoma cells
This study was supported by a Grant (H16-kokoro-024) to K.D. from the Ministry of Health, Labor, and Welfare, Japan. The authors thank Drs. Jiro Takata, Atsushi Yamauchi, Shinya Dohgu, Satoshi Kawatake, Toru Iwaki, and Kenta Teruya for their suggestions, and Ms. Kyomi Sasaki for manuscript preparation.
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