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Neuroprotective Properties of Quinone Reductase 2 Inhibitor M-11, a 2-Mercaptobenzimidazole Derivative
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Neuroprotective Properties of Quinone Reductase 2 Inhibitor M-11, a 2-Mercaptobenzimidazole Derivative
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Journal Article
Neuroprotective Properties of Quinone Reductase 2 Inhibitor M-11, a 2-Mercaptobenzimidazole Derivative
2021
Overview
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.
Publisher
MDPI AG,MDPI
Subject
/ Animals
/ Dose-Response Relationship, Drug
/ Drug Evaluation, Preclinical
/ Enzyme Inhibitors - administration & dosage
/ Enzyme Inhibitors - chemistry
/ Enzyme Inhibitors - pharmacology
/ Enzymes
/ Ligands
/ Male
/ Mice
/ Neuroprotective Agents - administration & dosage
/ Neuroprotective Agents - chemistry
/ Neuroprotective Agents - pharmacology
/ Pyrrolizidine Alkaloids - pharmacology
/ Quinone Reductases - antagonists & inhibitors
