*5.2. Mode of Action of Atovaquone and Hydroxynaphtoquinones*

The mode of action of atovaquone and other hydroxynaphtoquinones is based on the inhibition of mitochondrial cytochrome *bc1* complex via the competitive inhibition of ubiquinol binding [98,99]. Consequently, atovaquone induces the collapse of the mitochondrial membrane potential, blocking the energy supply of the parasites, leading to parasite death [100,101]. Concomitantly, the ubiquinol accumulation due to the inhibition of its binding site generates also a significant amount of superoxide radicals (ROS), as was shown in cancer cells and *Plasmodium* [16,102].

#### *5.3. Mode of Action of Artemisinin: The Role of Endoperoxide*

Artemisinins are at the forefront of the war against malaria and are used in combination with other antimalarial agents in artemisinin-based combination therapies (ACTs) [103,104]. This class of compounds, which includes arteether, artemether, artesunate, and dihydroartemisinin [105], is characterized by the presence of an endoperoxide group that is responsible for the antimalarial activity.
