*5.1. Mode of Action of Chloroquine and Other Quinolines*

Quinolines have been reported to inhibit the polymerization of heme to hemozoin in food vacuoles, leading to the accumulation of heme [94]. Moreover, chloroquine and other quinolines differently inhibit the peroxidative degradation of heme by H2O2, hence increasing heme accumulation and consequently enhancing heme-catalyzed reactions, leading to the production of ROS and parasite death [44,95]. The formation of the heme–FeIII adduct with chloroquine in the food vacuole leads to its diffusion into the cytosol, where the complex is dissociated, releasing heme in the parasite cytosol and hence promoting the redox cycling of FeIII to FeII, which enhances ROS generation [96]. This has also been reported for quinine [96] and may apply to other quinolines. Other purported modes of action of quinolines include the inhibition of the peroxidase-like activities of heme, leading to the accumulation of H2O2, which interacts with heme to form radicals [97]. Reviewed reports about the mode of action of quinolines have revealed their varying levels of activity that trigger ROS generation [44,94,96].
