A Quinoxaline 1,4-Dioxide Activates DNA Repair Systems in <em>Mycobacterium smegmatis</em>: A Transcriptomic Study
Listed in
This article is not in any list yet, why not save it to one of your lists.Abstract
In 2022, the World Health Organization reported that tuberculosis (TB) was the second leading cause of death globally from a single infectious agent, following COVID-19. The development of new antitubercular agents with novel mechanisms of action for use in complex TB therapy is considered a key approach to combating TB. In this study, we examined the gene expression profile of M. smegmatis when exposed to a promising antituberculosis agent, quinoxaline 1,4-dioxide (QdNO) 7-chloro-2-(ethoxycarbonyl)-3-methyl-6-(piperazin-1-yl)quinoxaline-1,4-dioxide-1 (LCTA-3368). We investigated how the bacterial response changed with different doses (1/4 × MIC, 1/2 × MIC, and 1 × MIC) and durations (30 minutes and 90 minutes) of treatment with the drug. Our analysis revealed significant upregulation of genes involved in DNA repair and replication processes, as well as changes in the expression of 95 genes encoding proteins with oxidoreductase activity. These findings support the proposed mechanism of antibacterial action of QdNOs, which is associated with the formation of free radicals leading to DNA damage.