title: Synthesis and biological evaluation of 5-nitropyrimidine-2,4-dione analogues as inhibitors of nitric oxide and iNOS activity.
abstract: Fifty two compounds based on 5-nitropyrimidine-2,4-dione moiety have been synthesized and evaluated for their inhibitory potency on the production of nitric oxide. Among them, compound 36 inhibited the production of nitric oxide (IC50 : 8.6 μm) on lipopolysaccharide-induced RAW 264.7 cells and inducible nitric oxide synthase activity (IC50 : 6.2 μm), as well as exerted no potential cytotoxicity (IC50 > 80.0 μm). Docking study confirmed that compound 36 was an inducible nitric oxide synthase inhibitor with perfect binding to the active site of inducible nitric oxide synthase. At a dose of 10 mg/kg, oral administration of 36 possessed protective properties in carrageenan-induced paw edema of male ICR mice.
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, 610041, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Ma
authors.forename: Linhong
authors.initials: L
authors.lastname: He
authors.forename: Lei
authors.initials: L
authors.lastname: Lei
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Liang
authors.forename: Kai
authors.initials: K
authors.lastname: Lei
authors.forename: Ronghong
authors.initials: R
authors.lastname: Zhang
authors.forename: Zhuang
authors.initials: Z
authors.lastname: Yang
authors.forename: Lijuan
authors.initials: L
authors.lastname: Chen
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001665:Binding Sites; D002351:Carrageenan / Q000633:toxicity; D020134:Catalytic Domain; D002460:Cell Line; D004353:Drug Evaluation, Preclinical; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D006860:Hydrogen Bonding; D008070:Lipopolysaccharides / Q000633:toxicity; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D062105:Molecular Docking Simulation; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011744:Pyrimidinones / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D013343:Styrenes / Q000138:chemical synthesis* / Q000627:therapeutic use / Q000633:toxicity; D014498:Uracil / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000627:therapeutic use / Q000633:toxicity
chemical_list: C000602518:5-nitro-6-(3-nitrostyryl)pyrimidine-2,4(1H,3H)-dione; D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D011744:Pyrimidinones; D013343:Styrenes; D009569:Nitric Oxide; D014498:Uracil; D002351:Carrageenan; D052247:Nitric Oxide Synthase Type II
keywords: 5-nitropyrimidine-2,4-dione; docking study; inducible NOS; nitric oxide production; paw edema