Quinolines antimalarial activity, toxicity

Interaction of marine isonitriles derivatives with heme was shown to inhibit the transformation of heme into / -hematin and then hemozoin, a polymer produced by Plasmodium in order to neutralize the toxic (detergent-like) free heme produced in the food vacuole. In addition, isonitriles were shown to prevent both the peroxidative and glutathione-mediated destruction of heme under conditions that mimic the environment within the malaria parasite. In summary, isonitriles, similarly to quinoline antimalarials [38], exert their antiplasmodial activity by preventing heme detoxification. 

It has been underlined that the antimalarial activity of quinoline-based drugs (quinine, chloroquine, mefloquine) also depend on their interactions with heme, thus preventing aggregation of toxic heme released during proteolysis of hemoglobin by die parasite. In vitro, efficient quinolines block the aggregation... 

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