Afobazole metabolite M-11 inhibits quinone reductase 2
https://doi.org/ 10.24411/2587-7836-2018-10020.
Abstract
Resume. Objective. Inhibition of quinone reductase 2 (NQO2) is a perspective target to achieve neuroprotective effect. Anxiolytic drug afobazole (5-Ethoxy-2-[2-(morpholino)-ethylthio]benzimidazole dihidrochloride) and its main metabolite M-11 (2-[2-(3-oxomorpholin-4-il)-ethylthio]-5-ethoxybenzimidazole hydrochloride) can interact with melatonin dependent regulatory site of NQO2. Previously we have figured that afobazole inhibits NQO2. However, the role of interaction between M-11 and NQO2 is unclear. Aim. To study the effect of M-11 on activity of NQO2. Methods. The influence of M-11 on activity of human recombinant NQO2 (hNQO2) was measured utilizing fluorescent spectroscopy. Results. M-11 inhibits hNQO2 in concentrations of 0.5 and 1.0 mM, decreasing enzymatic reaction velocity on 12 and 24 % respectively. In same concentrations, M-11 is inferior to afobazole. Conclusion. Compound M-11 inhibits NQO2 and can be used to study pharmacological effects of afobazole caused by interaction with regulatory site of enzyme.
About the Authors
I. A. Kadnikov
FSBI «Zakusov institute of Pharmacology»
Russian Federation
Russian Federation
M. V. Voronin
FSBI «Zakusov institute of Pharmacology»
Russian Federation
Russian Federation
S. B. Seredenin
FSBI «Zakusov institute of Pharmacology»
Russian Federation
Russian Federation
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Review
For citations:
Kadnikov I.A., Voronin M.V., Seredenin S.B. Afobazole metabolite M-11 inhibits quinone reductase 2. Pharmacokinetics and Pharmacodynamics. 2018;(3):27-30. (In Russ.) https://doi.org/ 10.24411/2587-7836-2018-10020.
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