1. Academic Validation
  2. Neuroprotective Properties of Quinone Reductase 2 Inhibitor M-11, a 2-Mercaptobenzimidazole Derivative

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

  • Int J Mol Sci. 2021 Dec 2;22(23):13061. doi: 10.3390/ijms222313061.
Mikhail V Voronin 1 Ilya A Kadnikov 1 Liana F Zainullina 1 Ilya O Logvinov 1 Ekaterina R Verbovaya 1 Tatyana A Antipova 1 Yulia V Vakhitova 1 Sergei B Seredenin 1
Affiliations

Affiliation

  • 1 Department of Pharmacogenetics, Federal State Budgetary Institution "Research Zakusov Institute of Pharmacology", Baltiyskaya Street 8, 125315 Moscow, Russia.
Abstract

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.

Keywords

2-mercaptobenzimidazole derivative; BNAH; HT-22 cells; NQO2; NQO2 inhibitors; ROS; S29434; adrenochrome; apoptosis; comet assay.

Figures
Products