UCF Research Holds Promise for Fighting Malaria

UCF researchers are making advances in finding novel and more effective treatments for malaria, by using cancer drugs and fungi.

With two $3.8 million grants from the National Institutes of Health, Debopam Chakrabarti, an infectious disease specialist at the UCF College of Medicine, has been researching new ways to combat drug-resistant malaria. The disease kills more than 600,000 people per year globally, and disproportionately impacts women and young children under the age of 5. As part of his research efforts, Chakrabarti recently published two new investigative studies in leading scientific journals.

The first study, published in the Journal of Medicinal Chemistry, examined the potential for repurposing existing cancer drugs as antimalarial therapies. The research was in partnership with Ratna Chakrabarti, a UCF cancer molecular biologist, Nathanael Gray, a cancer therapeutics researcher at Stanford University, and Elizabeth Winzeler, a malaria drug expert from the University of California-San Diego.

In Chakrabarti’s lab, doctoral researcher Monica Bohmer and postdoctoral fellow Flore Nardella screened several human kinase inhibitors used in cancer treatment and identified Compound 1 as a leading antimalarial agent that cured infected mice, and prevented the parasite that causes malaria from infecting cells in the first place.

Continuous genetic mutations that parasite, Plasmodium, makes it increasingly resistant to current drugs. As a result, new and more effective drugs are long overdue, especially with malaria deaths increasing significantly over the last few years.

“Our results are significant and could provide a promising solution for malaria prevention and treatment, particularly due to the compound’s low required dosage which will also reduce likelihood of any side effects,” Chakrabarti says.

Repurposing cancer drugs for malaria is essentially a “piggyback approach,” that would fast-track the process of getting the drug on the market as these compounds already have a long history of data on safety, toxicity and pharmacology and are already FDA approved.

Chakrabarti noted there is also a need for new prophylactic drugs to prevent malaria infection. About 2,000 cases of malaria are diagnosed in the United States each year, with most cases occurring in travelers returning from countries in sub-Saharan Africa and South Asia where malaria transmission frequently occurs.

“There are only two prophylactic drugs right now used in the U.S. for travelers to these areas,” Chakrabarti says. “One requires doses taken daily over several weeks and the other has neurological side effects. So better prophylactics with little or no side effects are needed.”

The second study published in Cell Chemical Biology examined the use of fungus-derived compounds to kill the malaria parasite. Partnering with Robert Cichewicz, a natural-product chemist from the University of Oklahoma and UCF postdoctoral fellow Jennifer Collins, Chakrabarti’s lab screened approximately 19,000 fungal species grown in Cichewicz’s lab. From these efforts, they identified antimalarial properties in a class of compounds called peptaibols — modified peptides produced by fungi.

Plasmodium cells ingest hemoglobin from blood to provide the nourishment they need to survive. Chakrabarti and the researchers found that the peptaibols work by changing the membrane structure of Plasmodium digestive vacuole which prevents it from digesting hemoglobin, essentially starving the parasite to death.

The next phase of both studies will look at testing the compounds in humanized animal models, along with further exploring their antimalarial mechanisms and properties.

“Both of these studies are a step in the right direction in the campaign to eliminate malaria globally and with this approach, we hope to have better drugs available sooner,” Chakrabarti says.

Chakrabarti has been researching malaria at UCF for more than 25 years. A Pegasus Professor in the Burnett School of Biomedical Sciences, he joined the university in 1995 and was one of the first UCF faculty members to receive an NIH grant. He received his doctorate in biochemistry from the University of Calcutta and completed post-doctoral training in molecular biology at the University of Nebraska-Lincoln.