Maleimides consist of an important class of compounds easily synthesized with multiple functional group modification that provides expressive pharmacological properties including, antitumoral activity, mediated mainly by oxidative stress. For this reason, the present study was designed to evaluate the cytotoxicity and the role of
reactive oxygen species (ROS) in
maleimide-induced cell death. Cell viability assays were performed to determine the cell death type in
leukemia cell line induced by the compounds. The oxidative stress in maleimidetreated cells was characterized by
antioxidant enzymes activities, intracellular ROS generation, and lipid peroxidation. In addition, we evaluated mitochondrial membrane potential and
ATP level.
Maleimide derivatives exhibited cytotoxic effects in
leukemia cells with significantly increased ROS generation. However, cell viability was partly restored by
catalase-treated cells.
Caspases activities and
caspase-independent key genes related to apoptosis were not altered by
maleimides, suggesting
necrosis as the main cell death process.
Maleimide-induced
necrosis was associated with oxidative stress, as an imbalance between ROS levels and
glutathione reductase (GR) activity. This damage was also demonstrated by loss of mitochondrial membrane potential (
MMP) and
ATP depletion in cells treated with
maleimide derivatives. These findings strongly confirmed that
maleimide derivatives promoted cell death in
leukemia cells triggered by oxidative stress, indicating that these compounds might be promising
antitumor agents or lead molecules.