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Synthesis and Biological Evaluation of 5‐Nitropyrimidine‐2,4‐dione Analogues as Inhibitors of Nitric Oxide and i NOS Activity
Author(s) -
Ma Liang,
He Linhong,
Lei Lei,
Liang Xiaolin,
Lei Kai,
Zhang Ronghong,
Yang Zhuang,
Chen Lijuan
Publication year - 2015
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12386
Subject(s) - nitric oxide , nitric oxide synthase , chemistry , lipopolysaccharide , moiety , cytotoxicity , pharmacology , biochemistry , carrageenan , stereochemistry , in vitro , biology , organic chemistry , immunology
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 (IC 50 : 8.6 μ m ) on lipopolysaccharide‐induced RAW 264.7 cells and inducible nitric oxide synthase activity (IC 50 : 6.2 μ m ), as well as exerted no potential cytotoxicity (IC 50 > 80.0 μ m ). 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.