Quinoxaline 1,4-di-N-Oxide Derivatives: Are They Unselective or Selective Inhibitors?

Background: For decades, the quinoxaline 1,4-di-N-oxide ring has been considered a privileged structure to develop new antibacterial, antitumoural, and antiprotozoal agents, among others; however, its mechanism of action is not clear. Objective: The main aim of this mini-review was to analyze the mechanism of action of quinoxaline 1,4-di-N-oxide derivatives reported as antibacterial, antitumoural, and antiprotozoal agents. Results: Initially, the mechanism of action of quinoxaline 1,4-di-N-oxide derivatives against bacteria, tumoural cell lines, and parasites have been described as nonspecific, but recently, the results against different organisms have shown that these compounds have an inhibitory action on specific targets such as trypanothione reductase, triosephosphate isomerase, and other essential enzymes. Conclusion: In summary, quinoxaline 1,4-di-N-oxide is a scaffold to develop new antiMycobacterium tuberculosis, antitumoural and antiprotozoal agents; however, understanding the mechanism of action of quinoxaline 1,4-di-N-oxide derivatives in each microorganism could contribute to the development of new and more potent selective drugs.