Griffith University scientists have helped discover new compounds which could help block the transmission of the deadly disease malaria.
A team of Griffith researchers has found a novel class of compounds, the hexahydro quinoline (HHQ), with potent activity against the parasite stages responsible for the clinical symptoms of malaria and its transmission to mosquitoes.
Malaria is still a leading cause of death, with 212 million new cases and 429 000 malaria deaths recorded worldwide in 2015, 90% of which are in Africa. A major obstacle in eradicating the disease is wiping out the sexual forms of the malaria parasites, the gametocytes.
While not responsible for the clinical symptoms, gametocytes are essential for the continued transmission of malaria, as these are the parasite stages taken up by the mosquito.
Gametocytes are naturally insensitive to the antimalarial drugs routinely used for malaria therapy and therefore escape the killing action of the drugs, enabling the new infections to occur.
Scientific paper released
The findings have been revealed in Nature Microbiology released this week.
Professor Vicky Avery led the team at the Griffith Institute for Drug Discovery (GRIDD) who developed the high content imaging and biochemical approaches they subsequently used for screening a focussed compound library called the Novartis-GNF Malaria Box against the gametocytes.
“This outcome demonstrates the high quality drug discovery efforts undertaken by my team and the considerable benefits of collaborative research, as we could not have achieved what we did without the collective efforts of the international team behind this,” Professor Avery said.
Dr Leonardo Lucantoni
This work was supported by a Bill & Melinda Gates Foundation (BMGF) Global Health grant awarded to Professors Vicky Avery and David Fidock (Columbia University, New York).
The mode of action of the HHQ compounds was shown to be linked to a parasite protein responsible for transporting nutrients across the cell, called PfMDR1. This protein is also responsible for transporting several types of antimalarial drugs into the parasites, and mutations in its gene can confer multidrug resistance to the parasites. Interestingly, HHQ-resistant parasites generated in the laboratory were found to be more susceptible to these other classes of drugs.
“This finding provides the exciting possibility of using HQQ compounds as partner drugs for future antimalarial combination therapies with the ability to block malaria transmission and counter the development of drug resistance”, Dr Lucantoni said.