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Terpene isonitriles bind heme
The antimalarial activity of the compound shown, isolated from a marine sponge, stems from its ability to coordinate with pure heme, a recent study shows. Pure heme is formed when the malaria parasite feeds on hemoglobin. The product is toxic to the parasite, which disposes of it in various ways. The well-known quinoline antimalarials prevent these detoxification processes. Now, researchers have found that compounds of the type shown--terpene isonitriles--achieve the same effect to different degrees by forming a complex with pure heme. The complex prevents destruction of pure heme, allowing it to build up and damage proteins and lipids in the parasite. Through modeling studies and structure-activity analysis of a series of terpene isonitriles, the researchers establish that, in this compound class, a lipophilic core comprising at least a tricyclic frame and carrying an axial isonitrile group at C-7 is associated with the ability to bind pure heme
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