Background: Quinoxalines have shown a wide variety of biological activities including as antitumor agents.
The aims of this study were to evaluate the activity of quinoxaline 1,4-di-N-oxide derivatives on K562 cells, the
establishment of the mechanism of induced cell death, and the construction of predictive QSAR models.
Material and Methods: Sixteen esters of quinoxaline-7-carboxylate 1,4-di-N-oxide were evaluated for antitumor
activity on K562 chronic myelogenous leukemia cells and their IC50 values were determined. The mechanism of
induced cell death by the most active molecule was assessed by flow cytometry and an in silico study was conducted to
optimize and calculate theoretical descriptors of all quinoxaline 1,4-di-N-oxide derivatives. QSAR and QPAR models
were created using genetic algorithms.
Results & Conclusions: Our results show that compounds C5, C7, C10, C12 and C15 had the lowest IC50 of the
series. C15 was the most active compound (IC50= 3.02 μg/mL), inducing caspase-dependent apoptotic cell death via
the intrinsic pathway. QSAR and QPAR studies are discussed.