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New compounds show promise in fighting malaria and cancer

s research and that of other laboratories revealed that the peroxide (oxygen-oxygen) unit within artemisinin and within other antimalarial trioxane drugs causes the malaria parasites to self-destruct.

"We know that the malaria parasites digest hemoglobin in order to get nutrients, and in the process they release heme," Posner explained. "When the heme encounters the peroxide bond, a chemical reaction occurs. Powerful chemical species such as carbon-free radicals and oxidizing agents are produced, harming and eventually killing the parasites."

In the laboratory, several of the Posner trioxane compounds were compared against sodium artesunate the gold standard for malaria treatment in rodents. Administered intravenously, two of the new compounds outperformed the gold standard.

"One was six or seven times better, and the other was three or four times more effective, which is substantial," Posner said. "What's more, when the trioxanes were administered orally, it was found that one of ours is four times more effective. That's significant."

Lab testing also revealed that at least one of the trioxane compounds known as compound 7 seems to be even safer than sodium artesunate.

Testing of the Johns Hopkins trioxanes in rodent models for human prostate cancer in collaboration with the Roswell Park Cancer Institute in Buffalo, N.Y., was equally encouraging to the researchers, who are promoting the compounds as dual-use drug candidates.

In that laboratory, researchers pitted the potency of the trioxane compounds against two gold standard anticancer drugs, Gemzar and Adriamycin. They found that while trioxane compound 6 was comparable to the cancer-fighting action of Adriamycin, compound 5 appears to be nearly three times more powerful than that drug.

"Our learning from this is that trioxane dimers 5 and 6, and especially 6, are exciting not just for their antimalarial potential, but also for their anticancer potent
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Contact: Lisa DeNike
lde@jhu.edu
443-287-9960
Johns Hopkins University
24-Aug-2004


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