New series of antiprion compounds: pyrazolone derivatives have the potent activity of inhibiting protease-resistant prion protein accumulation.
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.
Kimata
Ayako
A
Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1, Tanabe-dori, Mizuho-ku, Nagoya, Aichi 467-8603, Japan.
Nakagawa
Hidehiko
H
Ohyama
Ryo
R
Fukuuchi
Tomoko
T
Ohta
Shigeru
S
Doh-ura
Katsumi
K
Suzuki
Takayoshi
T
Miyata
Naoki
N
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
D000975:Antioxidants; D016166:Free Radical Scavengers; D018620:PrPSc Proteins; D047069:Pyrazolones; D017665:Hydroxyl Radical; D013482:Superoxide Dismutase