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Office of News and Information
Johns Hopkins University
3003 N. Charles Street, Suite 100
Baltimore, Maryland 21218-3843
Phone: (410) 516-7160 | Fax (410) 516-5251

August 29, 2001
CONTACT: Michael Purdy


Researchers at The Johns Hopkins University have designed a new drug for malaria that has easily passed the first stage of preclinical testing in mice and rats.

Scientists will announce their successful results in Chicago on August 29, 2001 at the American Chemical Society's annual summer meeting. The results will also appear as an expedited article in the September 2001 issue of the Journal of Medicinal Chemistry.

"The new compound is known as a carboxyphenyl trioxane, and its therapeutic index, the measure of a drug's safety and efficacy in treating a disease, is very good," says Gary Posner, Scowe Professor of Chemistry in the Krieger School of Arts and Sciences at Hopkins. "In addition, it's water soluble and therefore easy to administer orally and intravenously."

Annually, malaria infects 300 to 500 million people and causes 1.5 to 3 million deaths. It is primarily spread by mosquito bites. The most commonly fatal strain of the malaria parasite is showing considerable resistance to current treatments, making development of new drugs a priority.

Posner worked with Theresa Shapiro, professor of Clinical Pharmacology at the Hopkins School of Medicine, and co-workers Michael Parker, Heung Bae Jeon, Mikhail Krasavin, and Ik-Hyeon Paik to synthesize and test antimalarial drugs in the laboratory. Posner and Shapiro are active in the organization of the new $100 million Malaria Research Institute at the University's Bloomberg School of Public Health.

Posner, who will present at a symposium in Chicago called "Advances in Controlling Parasitic Diseases," says results from first-stage testing of the drug's effectiveness and toxicity in mice and rats compared favorably to results from another water-soluble candidate for malaria treatment. That other drug is under development at the U.S. Walter Reed Army Institute of Research.

"There are some aspects where the Army's compound is better, and some where ours is better, and we hope that by showing that our carboxyphenyl trioxane has comparable potential we'll receive support for further animal testing of it," says Posner.

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.

Related web sites
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