Novel Anti-Malarial Drug Target Identified

n international team of scientists, led by researchers from the Department of Pediatrics at the University of California, San Diego School of Medicine, have identified the first reported inhibitors of a key enzyme involved in survival of the parasite responsible for malaria. Their findings, which may provide the basis for anti-malarial drug development, are currently published in the online version of the Journal of Medicinal Chemistry . Tropical malaria is responsible for more than 1.2 million deaths annually. Severe forms of the disease are mainly caused by the parasite Plasmodium falciparum , transmitted to humans by female Anopheles mosquitoes. Malaria eradication has not been possible due to the lack of vaccines and the parasite's ability to develop resistance to most drugs. The researchers conducted high-throughput screening of nearly 350,000 compounds in the National Institutes of Health's Molecular Libraries Small Molecule Repository (MLSMR) to identify compounds that inhibit an enzyme which plays an important role in parasite development: Plasmodium falciparum glucose-6-phosphate dehydrogenase ( Pf G6PD) is essential for proliferating and propagating P. falciparum. "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," said senior author Lars Bode, PhD, assistant professor in the UCSD Department of Pediatrics, Division of Neonatology and the Division of Gastroenterology, Hepatology and Nutrition.