A chemical that rid mice of malaria-causing parasites after a single oral dose may eventually become a new malaria drug if further tests in animals and people uphold the promise of early findings. The compound, NITD609, was developed by an international team of researchers.
“Although significant progress has been made in controlling malaria, the disease still kills nearly 1 million people every year, mostly infants and young children,” says NIAID Director Anthony S. Fauci, M.D. “It has been more than a decade since the last new class of antimalarials—artemisinins—began to be widely used throughout the world. The rise of drug-resistant malaria parasites further underscores the need for novel malaria therapies.”
Dr. Fauci adds that the compound “appears to target a parasite protein not attacked by any existing malaria drug, and has several other desirable features. This research is also a notable example of successful collaboration between government-supported scientists and private sector researchers.”
The study, in the Sept. 3, 2010 issue of Science, was led by Thierry T. Diagana, Ph.D., of the Novartis Institute for Tropical Diseases (NITD), and Dr. Winzeler. Dr. Winzeler is affiliated with The Scripps Research Institute and the Genomic Institute of the Novartis Research Foundation, La Jolla, Calif.
Work on what eventually became NITD609 began in Dr. Winzeler’s lab in 2007. Scientists screened 12,000 chemicals using an ultra-high throughput robotic screening technique customized to detect compounds active against Plasmodium falciparum, the most deadly malaria parasite. The screen identified a chemical with good parasite-killing abilities and the potential to be modified into a drug. Medicinal chemists at the NITD then synthesized and evaluated about 200 versions of the original compound to arrive at NITD609, which could be formulated as a tablet and manufactured in large quantities. NITD609 is one of a new class of chemicals, the spiroindolones, which have been described in recently published research by Dr. Winzeler and colleagues as having potent effects against two kinds of malaria parasites.
“From the beginning, NITD609 stood out because it looked different, in terms of its structure and chemistry, from all other currently used antimalarials,” says Dr. Winzeler. “The ideal new malaria drug would not just be a modification of existing drugs, but would have entirely novel features and mechanism of action. NITD609 does.”