An international team of scientists has developed a compound, ML276, that could be used to create a powerful anti-malaria drug. They claim that the compound blocks glucose-6-phosphate dehydrogenase (G6PD), a key enzyme involved in the survival of the malaria parasite plasmodium falciparum.
In 2011, nearly 2000 people in the UK died because of malaria. Malaria is mainly caused by the plasmodium falciparum parasite, which is transmitted to humans by female mosquito. The plasmodium falciparum parasite infects the red blood cells and the G6PD protects the parasite from oxidation stress. This occurs when there is an increase or decrease in the oxidation level in the red blood cells.
"The enzyme G6PD catalyses an initial step in a process that protects the malaria parasite from oxidative stress in red blood cells, creating an environment in which the parasite survives," said Lars Bode, PhD, assistant professor in the University of California, San Diego School of Medicine, in a statement.
Malaria eradication has not been possible due to lack of vaccines and the parasite's ability to develop resistance to most drugs. However, scientists have developed a compound that could be used to create a potent malaria drug.
To create the ML276 compound, scientists tested more than 350,000 compounds in the National Institutes of Health's Molecular Libraries Small Molecule Repository (MLSMR) to see which compounds could stop the parasite development.
Scientists found that ML276 compound stops the G6PD enzyme, which protects the malaria parasite.
"The parasitic form of the enzyme (PfG6PD) is what contributes the majority of G6PD activity in infected red blood cells. Because the parasite lives in the blood of a malaria-infected person, we tried to identifying compounds that inhibit the parasitic form but not the human form of the enzyme. We didn't want to interfere with the human form of the enzyme and risk potential side effects," Bode said.
He said ML276 represents the first reported selective PfG6PD inhibitor, which stops the growth of malaria parasites in cultured red blood cells - even those parasites that developed resistance to currently available drugs. "ML276 is a very promising basis for future drug design of new anti-malarial therapeutics," he said.