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Both compounds trace their roots to the work of Chinese organic chemists who 30 years ago isolated the pharmacologically active component of the plant artemisia, historically used by the Chinese as an herbal remedy for malaria.

With support from the National Institutes of Health since 1994, Posner's group has explored the details of how the active component of the herbal remedy fights malaria. Their research and that of other laboratories showed that the malaria parasite's metabolism creates products that react chemically with a peroxide (oxygen to oxygen) bond in the anti-malaria compound, generating harmful compounds such as oxidizing agents and carbon-free radicals that kill the parasite.

"Knowing the mechanistic details of how this happens gave us the insights we needed for rational design of new treatments," says Posner, who used his skills in what he calls "molecular architecture" to design molecules with improved malaria-fighting characteristics. The new carboxyphenyl trioxane is the best to emerge so far from hundreds of candidate molecules Posner's group has designed and synthesized.

Future plans include having a manufacturer produce a kilogram of the carboxyphenyl trioxane, which is completely synthetic, under "good manufacturing practice" conditions for testing in larger animals and in humans.

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Contact: Michael Purdy
mcp@jhu.edu
410-516-7906
Johns Hopkins University
29-Aug-2001