Unlike similar compounds tested against many other parasitic protozoa, the drug readily crosses into the red blood cells of malaria-infected mice and kills the malaria parasite. The drug works at very low concentrations with no observed toxicity to the mouse.
“We found that compounds that were really active had a very long hydrocarbon chain,” Oldfield said. “These compounds can cross the cell membrane and work at very low concentrations.”
The World Health Organization estimates that malaria killed 708,000 to 1.003 million people in 2008, most of them in Sub-Saharan Africa and Asia. The malaria parasite has evolved resistance to nearly every drug used so far to combat it, and while some of these drugs still work – especially when used in combination – drug-resistant malaria strains are always emerging.
“It’s important to find new drug targets because malaria drugs last only a few years, maybe 10 years, before you start to get resistance,” Oldfield said. “The parasites mutate and then you lose your malaria drug.”
“We are the first to show that the enzyme GGPPS is a valid target for malaria,” said study co-author Yonghui Zhang, a research scientist in Oldfield’s lab and inventor of the lead compound, BPH-703. “Our work gives a new direction to find new antimalarial drugs.”
Diana Yates | University of Illinois
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