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Evaluation of Nitric Oxide-Donating Properties of 11H-indeno[1,2-b]quinoxalin-11-one Oxime (IQ-1) by Electron Paramagnetic Resonance Spectroscopy.
Andrianov, Viacheslav V; Schepetkin, Igor A; Bazan, Leah V; Gainutdinov, Khalil L; Kovrizhina, Anastasia R; Atochin, Dmitriy N; Khlebnikov, Andrei I.
Afiliación
  • Andrianov VV; Zavoisky Physical-Technical Institute of the Russian Academy of Sciences, Kazan 420029, Russia.
  • Schepetkin IA; Department of Human and Animal Physiology, Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan 420008, Russia.
  • Bazan LV; Kizhner Research Center, Tomsk Polytechnic University, Tomsk 634050, Russia.
  • Gainutdinov KL; Department of Microbiology and Cell Biology, Montana State University, Bozeman, MT 59717, USA.
  • Kovrizhina AR; Zavoisky Physical-Technical Institute of the Russian Academy of Sciences, Kazan 420029, Russia.
  • Atochin DN; Zavoisky Physical-Technical Institute of the Russian Academy of Sciences, Kazan 420029, Russia.
  • Khlebnikov AI; Department of Human and Animal Physiology, Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan 420008, Russia.
Molecules ; 29(16)2024 Aug 12.
Article en En | MEDLINE | ID: mdl-39202899
ABSTRACT
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Oximas / Quinoxalinas / Óxido Nítrico Límite: Animals Idioma: En Revista: Molecules Asunto de la revista: BIOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Rusia Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Oximas / Quinoxalinas / Óxido Nítrico Límite: Animals Idioma: En Revista: Molecules Asunto de la revista: BIOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Rusia Pais de publicación: Suiza