Neuroprotective Properties of Quinone Reductase 2 Inhibitor M-11, a 2-Mercaptobenzimidazole Derivative

International Journal of Molecular Sciences

Ilya O. Logvinov¹  Yulia V. Vakhitova¹  Ilya A. Kadnikov¹  Ekaterina R. Verbovaya¹  Mikhail V. Voronin¹  Sergei B. Seredenin¹  Liana F. Zainullina¹  Tatyana A. Antipova¹ 

[1] Department of Pharmacogenetics, Federal State Budgetary Institution “Research Zakusov Institute of Pharmacology”, Baltiyskaya Street 8, 125315 Moscow, Russia;

关键词: NQO2;    adrenochrome;    BNAH;    ROS;    comet assay;    apoptosis;   

DOI  :  10.3390/ijms222313061

来源: DOAJ

【 摘 要 】

The ability of NQO2 to increase the production of free radicals under enhanced generation of quinone derivatives of catecholamines is considered to be a component of neurodegenerative disease pathogenesis. The present study aimed to investigate the neuroprotective mechanisms of original NQO2 inhibitor M-11 (2-[2-(3-oxomorpholin-4-il)-ethylthio]-5-ethoxybenzimidazole hydrochloride) in a cellular damage model using NQO2 endogenous substrate adrenochrome (125 µM) and co-substrate BNAH (100 µM). The effects of M-11 (10–100 µM) on the reactive oxygen species (ROS) generation, apoptosis and lesion of nuclear DNA were evaluated using flow cytometry and single-cell gel electrophoresis assay (comet assay). Results were compared with S29434, the reference inhibitor of NQO2. It was found that treatment of HT-22 cells with M-11 results in a decline of ROS production triggered by incubation of cells with NQO2 substrate and co-substrate. Pre-incubation of HT-22 cells with compounds M-11 or S29434 results in a decrease of DNA damage and late apoptotic cell percentage reduction. The obtained results provide a rationale for further development of the M-11 compound as a potential neuroprotective agent.

【 授权许可】

Unknown