Dr. Papireddy 'Reddy' Kancharla in his laboratory at Portland State University
Malaria remains one of the world's major public health problems. The disease, caused by the single celled Plasmodium parasite which is carried by female Anopheles mosquitoes, impacts 200 million clinical cases annually. It claims nearly half a million lives a year—mostly children under the age of five and pregnant women. A Portland State University (PSU) research study aims to develop a new, safe and powerful antimalarial drug.
Led by principal investigator Papireddy 'Reddy' Kancharla, a research assistant professor in the PSU chemistry department, the project's goal is to develop a medication that is potent against multiple life-cycle stages of the malaria parasite, and also has the potential to circumvent drug resistance and prevent relapsing infections.
Launched this year, the five-year project has been awarded $3.1 million in funding by the National Institutes of Health (NIH). Joining Kancharla on the project team are PSU chemistry research professor Jane X. Kelly and Alison Roth, a Research Microbiologist in the Experimental Therapeutics Branch at Walter Reed Army Institute of Research.
"This study is particularly exciting because our lead drug candidates not only showed promising blood stage and liver stage antimalarial activities, but in addition inhibited the dormant form of malaria parasites found in liver cells, which is seldom encountered in antimalarial compounds," said Kancharla.
BACKGROUND
Despite worldwide attention on the eradication of malaria, prevention and treatment of the disease remain difficult. This is partly due to Plasmodia's emerging resistance to the currently available antimalarials, and partly due to the absence of a clinically effective vaccine.
Because of these and other factors, there is "an urgent and continuous need for safe, affordable and novel antimalarial drugs," according to the project abstract.
Kancharla and his team have developed prodiginine natural products as novel antimalarials that are effective against multiple life-cycle stages of the malaria parasite. Their prodiginine drug compounds have unique chemical structures as compared to existing antimalarials and they likely operate by new mechanisms.
THE RESEARCH
The specific goal of this project is to conduct lead optimization studies to produce candidates of novel prodiginines that demonstrate enhanced antimalarial activity in rodents with good pharmacokinetic properties and an acceptable safety profile. This work is now well underway in Kancharla's laboratory.
For more details about the project, see the NIH funding announcement. To learn about other chemistry work being done at PSU, check out the Kancharla Lab website or head over to the chemistry department site.