Foraging the seas of Panama all the way to the Eastern Cape of South Africa, she brings marine organisms back to Oregon State University to unlock the compounds’ hidden power in the hopes of finding targets that shoot down cancer cells.
McPhail, an associate professor of medicinal chemistry in the School of Pharmacy, is trying to find compounds in natural products that can help fight cancer.
Natural product chemists look for new chemical diversity in the same way that we think about looking for new biological diversity.
As many as 70 percent of cancer drugs are derived from natural products, like coibamide — a molecule that comes from a byproduct of bacteria found in waters around the Island of Coiba off the coast of Panama that attacks brain cancer cells.
“When we refer to a natural product, we are really talking about a single pure compound, a substance that only comprises one-type of chemical compound, and those are very small molecules,” McPhail said.
McPhail’s research group is excited about two compounds they’ve discovered.
One of the compounds McPhail’s team discovered as a part of the International Cooperative Biodiversity Groups program in Panama was back in 2008. The compound coibamide comes from a cyanobacterium, a blue-green algae found in the waters off the coast of Coiba. The island was recently declared a UNESCO World Heritage Site because of its biodiversity.
The group has collaborated with Jane Ismael, associate professor of pharmacology in the department of pharmaceutical sciences, to examine more closely how coibamide kills cancer cells.
Coibamide has a unique mechanism called autophagy, allowing it to eat its way through the cell.
“This mechanism is actually really hot in the field of cancer cell biology,” McPhail said.
Ismael’s lab has carried out initial mouse studies into the effectiveness of coibamide.
“We’re working a lot with brain cancers because coibamide seems to be very good at inhibiting and killing these brain cancer cells,” McPhail said. “Brain cancer is known to be highly invasive and an aggressive cancer that is difficult to treat.”
A small tumor is implanted into the flank of the mouse, and then a researcher injects coibamide into the tumor to see if the tumor stops growing and examine side effects.
McPhail’s group found a second group of compounds from a rare “tunicate” that is only found off the Eastern Cape coast of South Africa.
Tunicates look like big sponges. They are filter feeders that stick onto reefs and are exposed to a huge diversity of organisms.
These big sponge-like masses makes compounds that McPhail’s lab named “mandelalides,” after former South African President Nelson Mandela.
“Tunicates are just big bags of bacteria,” McPhail said. “The bacteria are really the unsurpassed chemists.”
Back in the labs, researchers use spectroscopy, the firing of powerful lasers directly at the compounds, in order to determine their unique structures.
Mandelalides appear to have potent cancer cell toxins.
This research is challenging in part because researchers struggle with a limited supply of the natural compounds.
“The problem with natural products, always, is supply,” McPhail said. “There are simply never enough compounds to carry out studies.”
Collaboration with Rich Carter, a professor and chair in the department of chemistry, may be the answer to this compound shortage.
Carter’s lab is working to develop a synthetic version of these compounds.
“That would give us enough to do more biological studies in order to work out exactly how these compounds act, and how selective they might be for some cancer cells over other cancer cells,” McPhail said.
These collaborations are key to successful research.
“What is the point for us to sit here in our little lab, crunching away, finding another incredible structure and working out what that structure is?” McPhail asked. “With collaboration, we can really be able to understand what the function of these compounds is in nature.”