New insights into clinically used malaria drug offers hope 

Griffith University researchers have discovered that a commonly used antimalarial drug has significantly better activity against malaria parasites than previously thought, which could change the way the drug is used.

Around half the worlds’ population is at risk of malaria parasite infection and of the ~440,000 sufferers who die each year, around 80 per cent are young children who are not strong enough to fight off the killer parasite.

Prof Kathy Andrews.

Malaria researchers Professor Kathy Andrews and Associate Professor Tina Skinner-Adams, both from the Griffith Institute for Drug Discovery (GRIDD), led the work together with chemistry collaborators from Australia’s Commonwealth Scientific and Industrial Research Organisation (CSIRO).

The team found the antimalarial drug proguanil had significantly better activity against malaria parasites in vitro than previously thought.

Proguanil has been used as part of a malaria combination drug calledMalarone®for decades. While a benefit of proguanil is that it improves the activity of its partner drug (atovaquone), the activity of proguanil itself was thought to be poor.

“We are very excited about this finding,” GRIDD Acting Director Prof Andrews said.

“For decades there have been questions about the mode of action of proguanil against malaria parasites.

“Our work sheds light on how this drug works, showing that it has potent, but ‘slow’, parasite killing. This had not been researched previously and is important new information that may inform how proguanil is used currently and in the future.”

A/Prof Tina Skinner-Adams.

The Griffith and CSIRO team have also designed and tested a new version of proguanil that may be an alternative option as a partner drug for malaria.

Proguanil can be chemically changed by the body into a different drug called cycloguanil. However, this process varies in different people. In addition, parasite resistance to cycloguanil is widespread.

The new version of proguanil cannot be chemically changed by the body, which may offer advantages.

“We hope that a new version of proguanil that cannot be changed in the body to cycloguanil may be a new drug combination option in the future,” A/Prof Skinner-Adams said.

The work was published this week in the Nature Publishing GroupjournalCommunications Biology.

The Griffith led team also includes international researchers from the University of California in San Diego, Columbia University in New York and the Medicines for Malaria Venture in Geneva.

The work was funded by the National Health and Medical Research Council.

ENDS