A team led by scientists from the Genomics Institute of the Novartis Research Foundation and the Scripps Research Institute has discovered a family of compounds that could lead to a new generation of antimalarial drugs capable of not only alleviating symptoms but also preventing the disease.
The discovery of the imidazolopiperazines (IZPs) has been published in Science, and the dual-acting compounds target both liver and blood infections, attacking the Plasmodium parasite at both stages in its reproduction cycle. Most antimalarial drugs are only effective during the blood stage, and those that do work in the liver have notable side effects.
To find compounds to act against the parasite in more than one stage of its lifecycle, researchers screened thousands of candidates that were already known to act against malaria parasites in the blood. Only 15% looked as if they might also work in the liver and when all the data was analysed, multiple members of this imidazolopiperazine family were active in blood and liver stages.
The imidazolopiperazine family of compounds was especially attractive, say the researchers, because it was chemically unrelated to existing antimalarials, and therefore less likely to run into problems with existing resistance.
Support for the study came from the Wellcome Trust, the Medicines for Malaria Venture, the Genomics Institute of the Novartis Research Foundation, the Swiss Tropical and Public Health Institute and the Novartis Institute for Tropical Diseases.