Quinoline antimalarials: mechanisms of action and resistance and prospects for new agents.
M Foley, L Tilley
Pharmacology & Therapeutics | Published : 1998
Quinoline-containing antimalarial drugs, such as chloroquine, quinine and mefloquine, are mainstays of chemotherapy against malaria. The molecular basis of the action of these drugs is not completely understood, but they are thought to interfere with hemoglobin digestion in the blood stages of the malaria parasite's life cycle. The parasite degrades hemoglobin, in an acidic food vacuole, producing free heme and reactive oxygen species as toxic by-products. The heme moieties are neutralized by polymerisation, while the free radical species are detoxified by a vulnerable series of antioxidant mechanisms. Chloroquine, a dibasic drug, is accumulated several thousand-fold in the food vacuole. The..View full abstract