title: Chelating compound, chrysoidine, is more effective in both antiprion activity and brain endothelial permeability than quinacrine.
abstract: 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.
authors.affiliation: Department of Prion Research, Tohoku University Graduate School of Medicine, 2-1 Seiryo-cho, Aoba-ku, Sendai 980-8575, Japan. doh-ura@mail.tains.tohoku.ac.jp
authors.forename: Katsumi
authors.initials: K
authors.lastname: Doh-ura
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Tamura
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Karube
authors.forename: Mikihiko
authors.initials: M
authors.lastname: Naito
authors.forename: Takashi
authors.initials: T
authors.lastname: Tsuruo
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Kataoka
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000187:drug effects*; D002614:Chelating Agents / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D018620:PrPSc Proteins / Q000378:metabolism; D017096:Prion Diseases / Q000517:prevention & control; D011328:Prions / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000378:metabolism; D011485:Protein Binding; D011796:Quinacrine / Q000494:pharmacology* / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000378:metabolism; D014407:Tumor Cells, Cultured; D010128:p-Aminoazobenzene / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D002614:Chelating Agents; D018620:PrPSc Proteins; D011328:Prions; D011994:Recombinant Proteins; C005562:chrysoidine; D010128:p-Aminoazobenzene; D011796:Quinacrine