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Scripps Research scientists identify new class of antimalarial compounds
Date:11/17/2011

a complicated lifecycle in two hostsmosquitoes and humans (or other vertebrate). When a malaria-infected mosquito feeds on a person, the parasite enters the human body. Within 30 minutes, the parasite has infected liver cells, where it develops for about eight days without causing noticeable symptoms. In some cases it can even go into hiding in the liver and persist for several months to years.

When this period is over, however, the parasite (now in a different form) leaves the liver and enters red blood cells, where it grows and multiplies. When the infected red blood cells eventually burst, the parasite and Plasmodium toxins are released into the bloodstream, and the person feels sick. Symptoms include fever, chills, headache, and other flulike symptoms; in severe cases, patients can experience convulsions, coma, and liver and kidney failure, which can be fatal.

If a mosquito bites the infected person at this point, the parasite will enter the mosquito, where it will continue the cycle by maturing into a form that can infect the next human host.

Mining the Data

To find compounds to act against the parasite in more than one stage of its lifecycle, the team screened thousands of candidates that were already known to act against malaria parasites in the blood. Only 15 percent looked as if they might also work in the livera strong indication, Winzeler said, that "a lot of compounds that are active against blood stages probably aren't going to do anything about eliminating malaria."

The group then identified the strongest candidates for drug development by mining the data for groups of related compounds that all showed activity in the liver. In the end, they settled on a cluster related to the chemical imidazolopiperazine. "When we analyzed all of the data, we saw that multiple members of this imidazolopiperazine family were active in blood and liver stages," Winzeler said.

The imidazolopiperazine family of c
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Contact: Mika Ono
mikaono@scripps.edu
858-784-2052
Scripps Research Institute
Source:Eurekalert  

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