Each year, more than 1.2 million people die from tropical malaria, now researchers have identified inhibitors of a key enzyme that helps the parasite responsible for the disease survive.

The study, conducted by researchers from the Department of Pediatrics at the University of California, San Diego School of Medicine, is published online in the Journal of Medicinal Chemistry. The teams findings may help in the development of anti-malarial drugs.

The parasite Plasmodium falciparum, which can be transmitted to humans by female Anopheles mosquitoes, are usually responsible for more sever forms of the disease.

After screening nearly 350,000 compounds in the National Institutes of Health’s Molecular Libraries Small Molecule Repository (MLSMR), the researchers identified the compound Plasmodium falciparum glucose-6-phosphate dehydrogenase (PfG6PD) which is vital for proliferating and propagating P. falciparum.

Lars Bode, Ph.D., assistant professor in the UCSD Department of Pediatrics, Division of Neonatology and the Division of Gastroenterology, Hepatology and Nutrition, explained: “The enzyme G6PD catalyzes 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.”

According to the researchers, individuals who are naturally deficient in this enzyme are protected from the disease and its lethal symptoms.

Most of G6PD’s activity in infected red blood cells is due to the parasitic form of the enzyme (PfG6PD). The researchers wanted to identify compounds that block the parasitic form without affecting the enzyme’s human form, given that the parasite lives in the blood of malaria-infected people.

Bode said: “We didn’t want to interfere with the human form of the enzyme and risk potential side effects.”

Researchers in the laboratory of Katja Becker, Ph.D., at the Interdisciplinary Research Center at Justus-Liebig-University in Giessen, Germany created the first complete and function recombinant PfG6PD. Scientists led by Anthony Pinkerton, Ph.D., at Sanford-Burnham Medical Research Institute than used it to identify the lead compound, ML276.

According to the researchers, ML276 is the first selective PfG6PD inhibitor. It prevents malaria parasites from growing in cultured red blood evens, even in parasite’s that have developed resistance to existing malaria drugs. Bode, explained: “ML276 is a very promising basis for future drug design of new anti-malarial therapeutics.”

Written by Grace Rattue