Objectives: The pterocarpanquinone LQB-118, previously demonstrated to be effective in vivo via oral delivery, was investigated for its mechanism in selective parasite killing. Methods: Oxidative stress in Leishmania amazonensis was analysed by evaluating reactive oxygen species (ROS) production (2′,7′-dichlorodihydrofluorescein diacetate) and the loss of mitochondrial membrane potential (DCm) using rhodamine, JC-1 and MitoCapture. Ultrastructural analysis was performed using transmission electron microscopy (TEM). DNA fragmentation was evaluated using terminal deoxyribonucleotidyl transferasemediated dUTP nick-end labelling (TUNEL). Results: Treatment with LQB-118 induced ROS production in the promastigotes of L. amazonensis in a concentration- dependent manner for the first 4 h and was sustained for 24 h. TEM analysis revealed several alterations typical of apoptosis. Promastigotes presented a reduction of DCm after 24 h of incubation with 2.5 mM (18.7%), 5 mM (63.7%) or 10 mM (70.7%) LQB-118. A sub-G0/G1 cell cycle phenotype was observed in 21%– 83% of the promastigotes incubated with 1.25–10 mM LQB-118. Concentration-dependent DNA fragmentation was observed in promastigotes treated with 2.5–10 mM LQB-118, and selective DNA fragmentation was observed in intracellular amastigotes after 72 h with 2.5 mM treatment. Conclusions: Our results suggest that LQB-118 selectively induces ROS-triggered and mitochondria-dependent apoptosis in this parasite.