IQ-1 (11H-indeno[1,2-b]quinoxalin-11-one oxime) is a specific c-Jun N-terminal kinase (JNK) inhibitor with anticancer and neuro- and cardioprotective properties. Because aryloxime derivatives undergo cytochrome P450-catalyzed oxidation to nitric oxide (NO) and ketones in liver microsomes, NO formation may be an additional mechanism of IQ-1 pharmacological action. In the present study, electron paramagnetic resonance (EPR) of the Fe2+ complex with diethyldithiocarbamate (DETC) as a spin trap and hemoglobin (Hb) was used to detect NO formation from IQ-1 in the liver and blood of rats, respectively, after IQ-1 intraperitoneal administration (50 mg/kg). Introducing the spin trap and IQ-1 led to signal characteristics of the complex (DETC)2-Fe2+-NO in rat liver. Similarly, the introduction of the spin trap components and IQ-1 resulted in an increase in the Hb-NO signal for both the R- and the T-conformers in blood samples. The density functional theory (DFT) calculations were in accordance with the experimental data and indicated that the NO formation of IQ-1 through the action of superoxide anion radical is thermodynamically favorable. We conclude that the administration of IQ-1 releases NO during its oxidoreductive bioconversion in vivo.

中文翻译：

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电子顺磁共振波谱法评价 11H-茚并[1,2-b]喹喔啉-11-酮肟 (IQ-1) 的一氧化氮供体性质


IQ-1（11H-茚并[1,2-b]喹喔啉-11-酮肟）是一种特异性 c-Jun N 末端激酶 (JNK) 抑制剂，具有抗癌、神经和心脏保护特性。由于芳基肟衍生物在肝微粒体中经历细胞色素 P450 催化氧化为一氧化氮 (NO) 和酮，因此 NO 形成可能是 IQ-1 药理作用的另一个机制。在本研究中，使用 Fe2+ 络合物与二乙基二硫代氨基甲酸酯（DETC）作为自旋陷阱和血红蛋白（Hb）的电子顺磁共振（EPR）分别检测大鼠肝脏和血液中 IQ-1 的 NO 形成。 IQ-1 腹膜内给药（50 mg/kg）。引入自旋陷阱和 IQ-1 导致了大鼠肝脏中复合物 (DETC)2-Fe2+-NO 的信号特征。同样，自旋捕获组件和 IQ-1 的引入导致血液样本中 R 构象和 T 构象的 Hb-NO 信号增加。密度泛函理论（DFT）计算与实验数据一致，表明IQ-1通过超氧阴离子自由基的作用形成NO在热力学上是有利的。我们得出的结论是，施用 IQ-1 在体内氧化还原生物转化过程中会释放 NO。