Iron Helps Trigger Artemisinin’s Activity

The antimalarial drug artemisinin needs a helping hand from iron to kill malaria parasites, a team of Australian and U.S. researchers suggests (Proc. Natl. Acad. Sci. USA, DOI: 10.1073/pnas.1104063108). Artemisinin, which comes from wormwood, is a crucial ingredient in combination malaria treatments. But scientists are still debating how it works. Some chemists think artemisinin’s endoperoxide ring must be activated before it can destroy parasites. However, it’s not clear whether that activation comes from iron sources, such as hemoglobin, or whether activation is metal-free. Leann Tilley at La Trobe University, in Melbourne, and coworkers now lend additional evidence to the iron-dependent idea. When they blocked an enzyme in the malaria parasite’s process of digesting hemoglobin in order to prevent release of iron-containing species such as heme, the parasites became markedly less sensitive to artemisinin. The team also found that parasites suspend hemoglobin breakdown in response to artemisinin in an apparent attempt to circumvent the drug’s effects. These observations mean that endoperoxides lasting longer in the bloodstream than artemisinin might be effective antimalarials, because the parasite must degrade hemoglobin to survive and can forgo the process only for so long, Tilley says.