Effect of Afobazole on Activity of Quinone Reductase 2

• Published in: Pharmaceutical chemistry journal 2014, Vol.47 (10), p.514-516
• Main Authors: Kadnikov, I. A., Voronin, M. V., Seredenin, S. B.
• Format: Article
• Language: English
• Subjects: Active oxygen; Enzyme inhibitors; Enzymes; Fluorescence; Medicine; Nucleic acids; Organic Chemistry; Pharmacology/Toxicology; Pharmacy; Quinone
• ISSN: 0091-150X; 1573-9031
• DOI: 10.1007/s11094-014-0993-y

The anxiolytic drug afobazole exhibited neuroprotective activity in various experimental models in vitro and in vivo . Our previous research found that afobazole was an MT 3 receptor ligand (IC 50  = 9.9 × 10 –7  M), which is known as a regulatory site of quinone reductase 2 (NQO2). The interaction of afobazole with MT 3 receptors can be considered as a part of its neuroprotective mechanism. Therefore, the purpose of the present work was to study the effect of afobazole on NQO2 activity in vitro . The influence of afobazole on NQO2 activity was studied using fluorescence spectroscopy. Afobazole was a mixed-type NQO2 inhibitor with K i  = 2.54 × 10 –4  M, which was close to K i for the endogenous enzyme inhibitor melatonin (K i  = 3.9 × 10 –4  M). The inhibitory activity of afobazole on NQO2 that was observed under conditions where nerve tissue injury was accompanied by increased formation of quinone oxidation products of catecholamines and excess generation of active oxygen species could prevent oxidative damage of membrane structures, proteins, and nucleic acids, which produced a neuroprotective effect.