A compound that shows promise for drug-resistant malaria has been discovered by scientists at the Novartis Institute for Tropical Diseases (NITD) in collaboration with researchers from the Genomics Institute of the Novartis Research Foundation (GNF), the Swiss Tropical and Public Health Institute, and The Scripps Research Institute.
Published in Science the findings demonstrated that the antimalarial candidate spiroindolone NITD609 was effective against both strains of the malaria parasite, Plasmodium falciparum and P. vivax. Through a reportedly novel mechanism, NITD609 cleared plasmodium in a malaria mouse model and showed pharmacological properties compatible with a once-daily dosing regimen.
Despite significant advances in Plasmodium genome biology, the identification and validation of new drug targets has proven challenging. In the Science paper the research team outlines how they identified a potential target by finding mutations that decreased the parasite's sensitivity to a new compound class.
"Using a novel Plasmodium whole-cell assay, we were able to tap into the Novartis archive of 12,000 pure natural products and synthetic compounds to identify 275 compounds highly active against P. falciparum, the most prevalent and deadly form of malaria," notes Novartis Institute for Tropical Diseases’ Bryan Yeung, project team head.
"From this set all but 17 compounds were discarded for failing to meet pharmacological and efficacy standards. Of the remaining compound class, spirotetrahydro-beta-carbolines or spiroindolones have favorable physical and chemical properties for drug development as well as a mechanism of action distinct from the currently used therapies based on aminoquinolines and artemisinin derivatives."