title: New series of antiprion compounds: pyrazolone derivatives have the potent activity of inhibiting protease-resistant prion protein accumulation.
abstract: To find effective antiprion compounds, we synthesized and evaluated various pyrazolone derivatives. Seven of 19 compounds showed inhibition of PrP-res accumulation and the remarkably active compound 13 showed an IC50 value of 3 nM in both ScN2a and F3 cell lines. Findings from studies on physicochemical and biochemical properties suggest that the action mechanism of these compounds does not correlate with any antioxidant activities, any of hydroxyl radical scavenging activities, or any SOD-like activities.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1, Tanabe-dori, Mizuho-ku, Nagoya, Aichi 467-8603, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Kimata
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Nakagawa
authors.forename: Ryo
authors.initials: R
authors.lastname: Ohyama
authors.forename: Tomoko
authors.initials: T
authors.lastname: Fukuuchi
authors.forename: Shigeru
authors.initials: S
authors.lastname: Ohta
authors.forename: Katsumi
authors.initials: K
authors.lastname: Doh-ura
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Naoki
authors.initials: N
authors.lastname: Miyata
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D004578:Electron Spin Resonance Spectroscopy; D016166:Free Radical Scavengers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D017665:Hydroxyl Radical / Q000378:metabolism; D051379:Mice; D018620:PrPSc Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D047069:Pyrazolones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000975:Antioxidants; D016166:Free Radical Scavengers; D018620:PrPSc Proteins; D047069:Pyrazolones; D017665:Hydroxyl Radical; D013482:Superoxide Dismutase