Oxidative stress inducers as potential anti-leishmanial agents

Abstract

Targeting redox metabolism of the parasite may prove to be a rewarding strategy in leishmaniasis since it plays a crucial role in the survival of Leishmania parasites inside the host cells where they face intense oxidative stress. Enzymes involved in redox metabolism have been widely studied establishing their significance in survival and virulence of Leishmania. Moreover, the selective presence of some of these enzymes makes them validated drug targets in Leishmania. Kinetoplastids like Leishmania are one of the most primitive eukaryotes possessing a single large branched mitochondrion spanning the cell body of the parasite, and their survival depends on the proper functioning of this single mitochondrion, which makes them vulnerable to mitochondrial stress. Mitochondria are primary sites where intracellular reactive oxygen species (ROS) are generated by the electron transport chain composed of multi-protein complexes present in the inner mitochondrial membrane. Several leishmanicidal agents have been identified to induce oxidative stress and disrupt the structural as well as functional integrity of the mitochondrion, thereby triggering an apoptosis-like cell death in Leishmania. Here, we provide an overview of the role of the antioxidant defense mechanism in Leishmania and highlight the potential of compounds inducing oxidative stress for their development as new anti-leishmanial agents.