Researchers have discovered 10 new molecular structures withpharmaceutical potential in a species of red seaweed that lives in theshallow coral reef along the coastline of Fiji in the south PacificOcean.
Some of these natural compounds showed the potential tokill cancer cells, bacteria and the HIV virus, according to research atthe Georgia Institute of Technology. In fact, two of them exhibitanti-bacterial activity towards antibiotic-resistant Staphylococcusaureus at concentrations worth pursuing, though researchers don’t knowyet whether the concentrations of the compounds required to kill thebacterium would be harmful to humans.
The compound that wasisolated in the greatest abundance – named bromophycolide A by theresearchers – killed human tumor cells by inducing programmed celldeath (called apoptosis), a mechanism that is promising for developmentof new anti-cancer drugs, researchers noted.
The findings onthree of these compounds – called diterpene-benzoate natural products –are reported in the Oct. 12 online issue of the American ChemicalSociety journal Organic Letters. Information on the other compoundswill be published later.
The research, which is part of anenvironmental conservation, economic development and drug discoveryproject in Fiji, was primarily funded by the Fogarty InternationalCenter at the National Institutes of Health. Georgia Tech Professor ofBiology Mark Hay leads the project, which also aims to benefit theFijian government and villages, which own their local natural resourcesand will benefit monetarily if these natural resources becomemarketable drugs.
“We’re only at the test-tube level so far,”explained Julia Kubanek, a Georgia Tech assistant professor of biology,chemistry and biochemistry, who is the lead author on the paper. “Thenext step is to discover how these compounds work and then to studythem in a more complex model system.”
The U.S. pharmaceuticalcompany Bristol Myers Squibb is collaborating with Georgia Techresearchers to determine how some of these 10 compounds kill cancercells. Meanwhile, Georgia Tech has filed a provisional patent toprotect the discovery of these structures and small variations of them.
“Thesemolecular structures are curious in the way carbon atoms are attached,”Kubanek said. “It’s very unusual. They represent a new category oforganic molecules. It’s exciting as a biochemist to observe that livingorganisms have evolved the ability to synthesize such unique and exoticstructures compared to other molecules typically produced by seaweeds.”
Thesource of these new molecular structures is a red seaweed (Callophycusserratus) collected from four Fijian sites. Among the sites,researchers found variations in the molecular structures produced bythe species.
“There are chemical differences among populations ofthis seaweed species, even though two of the sites where it wascollected are only about 2 kilometers apart,” Kubanek noted. “… Thisshows us there are small, but valuable differences within species, andthis genetic biodiversity is important to protect as a resource for thefuture.”
Researchers have been analyzing extracts from about 200marine plant and invertebrate animal samples they collected from theFijian coral reef in June 2004 with the permission of the Fijiangovernment and local resource owners.
“Marine organisms makemolecules for their own purposes that we might co-opt for our own useas pharmaceutical agents,” Kubanek explained. “The organisms’ purposesinclude defense against predators, the ability to fight diseases, andthe production of chemical cues, such as those used for sexrecognition.”
Hay, Kubanek, and their colleagues collectedbaseball-sized samples of reef species that exhibit unusual growthand/or behavioral phenomena. Among their collection were soft corals,marine sponges, slugs, and green, red and brown seaweeds.
In thelab, researchers extracted these organisms using mixtures of organicliquids, which opened up the cells and dissolved the natural products.The organic liquids were then removed from the extract by evaporation,and small quantities of each extract were tested against a battery ofpharmaceutical drug targets, including malarial parasite,tuberculosis-causing bacteria, and several cancers.
Typically,these tests involve exposing live, disease-causing cells -- parasites,bacteria or cancer cells -- to an extract and then assessing cell deathcompared to cells that were not exposed to extracts. Georgia Techscientists then prioritized further study of extracts that had strongeffects on these disease-causing cells.
The Callophycus redseaweed was one of the first five species that researchers investigatedto identify the compounds within extracts that caused strong effectsagainst disease-causing cells. Anne Prusak, a former Georgia Techstudent and research technician, separated the new molecules from othercomponents of the extract by a process called chromatography, whichtakes advantage of the different chemical characteristics of compounds.
Finally,researchers used X-ray crystallography (work done at Emory Universityin Atlanta), nuclear magnetic resonance spectroscopy and mass spectralanalyses to determine how carbon, oxygen, bromine and hydrogen atomsconnected to make up the molecular structures of the 10 new naturalproducts.
Much research is left to do before any of thesecompounds are used to formulate a drug available on the market, Kubaneksaid. It typically takes at least a decade from the discovery of acompound to the marketing of a new drug. If that does happen in thiscase, Fijian villagers and the Fijian government would benefitfinancially from the discovery because of an agreement that is alreadyin place, she added.
Because of the long timeframe in getting adrug to market, the project in Fiji provides other immediateconservation and economic development benefits to villagers and thegovernment.
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