Antimalarial agents selective toxicity

As described in section 4.1, the DNA double helix must unwind to allow access ofthe polymerase enzymes to produce two new strands ofDNA. This is facilitated by DNA gyrase, the target of the quinolones. Some agents interfere with the unwinding of the chromosome by physical obstruction. These include the acridine dyes, of which the topical antiseptic proflavine is the most familiar, and the antimalarial acridine, mepacrine. They prevent strand separation by insertion (intercalation) between base pairs from each strand, but exhibit very poor selective toxicity. 

Artemisinin compounds clear parasites from the blood more rapidly than any other antimalarial agent, by a unique pharmacodynamic action. They are concentrated in parasitized erythrocytes, and structure-activity relations (see Chapter 2) suggest that their endoperoxide bridge is essential for the antimalarial effect. A critical step in the mechanism of action seems to be a hemin-catalyzed reduction of the peroxide moiety, which results in free radicals and reactive aldehydes that subsequently kill the malaria parasites. The hemin-rich internal environment of the parasites is assumed to be responsible for the selective toxicity of artemisinin toward these organisms. 

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