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Researchers Decode Structure of Promising Sea Compound

Researchers Decode Structure of Promising Sea Compound

Scientists at Creighton University and their colleagues at Scripps Institution of Oceanography at University of California, San Diego (UCSD), have deciphered a highly unusual molecular structure of a naturally produced, ocean-based compound. The discovery is giving new understanding of the function of mammalian nerve cells.

The findings are reported in the Aug. 27 online version of the journal Chemistry & Biology by principal co-investigators Thomas Murray, professor and chair of pharmacology at Creighton University School of Medicine in Omaha, and William Gerwick, professor of oceanography and pharmaceutical sciences at the Center for Marine Biotechnology and Biomedicine (CMBB) at Scripps Institution of Oceanography and UCSD Skaggs School of Pharmacy and Pharmaceutical Sciences.

Scripps scientists collected tiny photosynthetic sea organisms, called cyanobacteria (Lyngbya majuscula and Phormidiu gracilem), in Hoia Bay off Papua New Guinea in 2002. They recently discovered that the cyanobacteria produce a compound with a structure previously unseen in biomedicine. The compound, which the researchers have dubbed hoiamide A, offers a novel template for drug development.

In pharmacological tests conducted at Creighton University, hoiamide A was shown to interact with the same important therapeutic target as analgesic, antiarrhythmic, antiepileptic and neuroprotective drugs.

“Given that approximately 50 percent of currently prescribed drugs are either natural products or derivatives of them, the discovery of the novel structure of hoiamide A and its effects on brain neurons opens exciting new avenues for drug discovery,” Murray said.

Extractions of mixture of cyanobacteria species collected by the Scripps scientists were shown to have intriguing neurochemical properties in assays run at Creighton University’s School of Medicine. Gerwick and Murray’s laboratories then collaborated to isolate the neuroactive substance and characterize its extraordinarily complex chemical structure.

“Classically, what we know about the workings of the human nervous system has come largely from studies of different toxins on the function of model systems, such as in this case, the action of hoiamide A on nerve cells in petri dish cultures,” said Gerwick.

“The toxins serve as ‘molecular tools’ for manipulating cells at an extremely microscopic scale. Ultimately, by understanding how neurons work at this detailed level and having a set of tools such as hoiamide A, we can envision the development of new, more effective treatments for such diverse conditions as epilepsy, pain control and memory and cognition enhancement. The natural world still has many valuable molecules left for us to discover and hopefully develop into new classes of medicines.”

In addition to Gerwick and Murray, the paper was coauthored by Zhengyu Cao of Creighton University and Alban Pereira of Scripps CMBB.

The study was supported by the National Institutes of Health.