Andrianov, Viacheslav V.Schepetkin, Igor A.Bazan, Leah V.Gainutdinov, Khalil L.Kovrizhina, Anastasia R.Atochin, Dmitriy N.Khlebnikov, Andrei I.2024-10-232024-08Andrianov, V.V.; Schepetkin, I.A.; Bazan, L.V.; Gainutdinov, K.L.; Kovrizhina, A.R.; Atochin, D.N.; Khlebnikov, A.I. Evaluation of Nitric Oxide-Donating Properties of 11H-indeno[1,2-b]quinoxalin-11-one Oxime (IQ-1) by Electron Paramagnetic Resonance Spectroscopy. Molecules 2024, 29, 3820. https://doi.org/10.3390/ molecules291638201420-3049https://scholarworks.montana.edu/handle/1/18889IQ-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.en-UScc-byhttps://creativecommons.org/licenses/by/4.0/c-Jun N-terminal kinase (JNK) inhibitorelectron paramagnetic resonancenitric oxide donorspin traphemoglobinDFT calculationArticle10.3390/molecules29163820