1,3-selenazol-4-one derivatives inhibit inducible nitric oxide-mediated nitric oxide production in lipopolysaccharide-induced BV-2 cells.
Activated microglia extensively produce nitric oxide (NO) by inducing expression of inducible NO synthase (iNOS). NO plays a deleterious role in brain inflammation and neuronal death. In the present study, we investigated the effects of 1,3-selenazol-4-one derivatives (Sz-A, B, C, D and E) on NO production and iNOS expression in lipopolysaccharide (LPS)-induced BV-2 cells, a murine microglia cell line. Among these compounds, Sz-B and C remarkably inhibited LPS-induced NO production relative to that of Sz-A, D, and E at 5 microM in BV-2 cells. Sz-B and C dose-dependently inhibited NO production at 1, 5, and 10 microM without toxicity to BV-2 cells. Sz-B and C also dose-dependently suppressed iNOS expression at the same concentrations in LPS-induced BV-2 cells. This result suggests that Sz-B and C inhibit iNOS-mediated NO production in LPS-induced BV-2 cells. Structurally, Sz-B and C bear an ethyl or methyl group at the 5 positions of the 4-selenazolone skeletons, which could play an important role in inhibiting iNOS-mediated NO production.
Park
Young-Joon
YJ
Department of Physical Pharmacy, College of Pharmacy, Seoul National University, Korea.
Koketsu
Mamoru
M
Kim
Jeong Min
JM
Yeo
Joo-Hong
JH
Ishihara
Hideharu
H
Lee
Kwang-Gill
KG
Kim
Sun Yeou
SY
Kim
Chong-Kook
CK
D000818:Animals; D001393:Azoles / Q000138:chemical synthesis / Q000494:pharmacology*; D015153:Blotting, Western; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D009569:Nitric Oxide / Q000009:adverse effects / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D016566:Organoselenium Compounds / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship
C474089:2-(4-Methylphenyl)-1,3-selenazol-4-one; D001393:Azoles; D008070:Lipopolysaccharides; D016566:Organoselenium Compounds; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse