Chemistry and public health professors team up to develop medicine for malaria.

The Antarctic is literally the last place anyone might expect to look for a treatment for a tropical disease like malaria, but under a retreating glacier is exactly where USF chemist Bill Baker found a bright red sea sponge that holds the latest hope for a new treatment.

Working in conjunction with tropical disease expert Dennis Kyle in USF’s Department of Global Health, College of Public Health, Baker tested compounds from the sponge and found them to be active against both malaria and leishmaniasis, a parasitic disease spread by sandflies which causes skin infections. Leishmaniasis is of particular concern to U.S. troops serving in the Middle East, but also is prevalent in places like India, Bangladesh, Brazil and Sudan.

Dennis Kyle, left, and Bill Baker, work to isolate disease-fighting compounds found
within natural resources discovered on Baker’s research expeditions to Antarctica.

“Natural products are where drug discovery began,” says Baker, who has made a dozen trips to Antarctica in search of compounds that can cure diseases, including cancers. “This has been going on for over a century and much of the proverbial low-hanging fruit has been picked. Everything in your backyard has been studied. You have to go out to where the biodiversity is rich.”

Their findings on the sponge compounds’ effects on leishmaniasis were recently published in the Journal of Natural Products, the first study published from the collaboration of the two internationally leading scientists. Of the 70,000 individual organisms extracted from the vast collection of Antarctic and other life Baker and his colleagues will study, Kyle expects at least 50 different novel compounds will be identified as potential disease fighters.

For more than two decades, Baker, who came to USF in 2001, has scoured the world’s oceans in search of new organisms that might produce biopharmaceuticals. Kyle arrived at the university in 2006 following his groundbreaking work at the Infectious Disease Research Program at Walter Reed Army Institute of Research.

Their search focuses on the compounds produced in the natural world – the plants, fungi and microbes that may act against some of the world’s most fearsome diseases. Infusing new, faster technology and procedures – such as nuclear magnetic resonance spectroscopy and mass spectrometry studies – the collaboration holds the promise of tapping the vast and unknown potential of marine environments.

“It’s sort of a process where you are searching for a needle in a haystack,” Kyle says. “Bill and his students go out and find the part of the haystack that’s active.”

The discovery of a new compound from the Antarctic comes at a time when scientists are trying to grapple with the problem of drug-resistant parasites. Tropical disease experts are particularly alarmed at growing evidence that the parasite that causes malaria – Plasmodium falciparum – is becoming resistant to artemisinin, the most effective drug currently used to combat malaria.

If resistance to artemisinin drugs spreads, it will be a global disaster, Kyle explains.
The benefits of any newly discovered drug are substantial. A child dies of malaria every 30 seconds – and some one million people succumb to the disease each year. Leishmaniasis causes nearly 60,000 deaths each year, leaving those who survive it disfigured or with related health issues.

But if compounds can be gathered from far-flung parts of the world where those parasites would have had no exposure to them and thus no resistance, the opportunities for creating medicines that work more effectively and for longer periods of time increase, Baker and Kyle say.

Scientists are particularly interested in polar compounds since just three percent of the marine natural products have been culled from polar organisms and it remains an untapped source of potential medicines.

In the case of the Crella sponge, the organism was freeze-dried and once back at Baker’s laboratory in Tampa underwent a multi-step process to extract its chemistry so it could be examined, cataloged and then tested against disease in Kyle’s lab.

There, human red blood cells infected with parasites that cause malaria and leishmaniasis were treated with the compounds. Five new steroids, called norselic acids, that were isolated from the sponges were found to be active against the parasites.

The next step, Kyle says, is to continue testing the compounds in animal models and continuing to search through the Antarctic collection for more promising chemicals, testing those against the assays in Kyle’s lab to see which ones have an effect on disease.

“The nice thing is that it’s easy to throw out a lot of it quickly because of the assays we have constructed,” Kyle says. “It helps you focus on the ones that have the most potential.”

Story by Vickie Chachere, photos by Joseph Gamble/Reprinted courtesy of USF Magazine