by Chivas Owle
University of Florida College of Pharmacy
Class of 2013
This article will discuss the role of marine biological compounds in natural products chemistry. Natural products chemistry is the search for biological compounds found in nature that can be used for the benefit of humans, often pharmaceutically.
Even fully synthetic drugs often have their basis in a drug discovered in nature. Perhaps the most famous example of this is morphine, which is derived from the seedpods of the plant species Papaver somniferum. However many variations of the original compound (over 200 in this class of medication alone) have been made by medicinal chemists for a variety of reasons, although the most common modification is to increase or decrease potency.
Historically, this is how most pharmaceutical agents were discovered. In ancient times, great civilizations used what the local plants and animals provided for them. Until the 1920’s, virtually all remedies were discovered through trial and error using the local products that were available. Once more scientific forms of investigation became available, many individual compounds were isolated from extracts used by indigenous populations.
Many of the most commonly used drugs in the world such as aspirin, atropine, colchicine, digoxin, and many more were discovered this way. This process defined modern natural products chemistry for decades and indeed this sort of novel compound discovery continues to this day, and for good reason. Much research remains – the vast majority of terrestrial plants and animals have not been studied for any medicinal use.
The primary benefit of using compounds produced in nature is that they are “prescreened” through the process of natural selection and serve some purpose already. The trick is to figure out what that function is and if it can be harnessed for our benefit. This is the principle concern of researchers who gather organisms, perform organic chemistry techniques to isolate the individual compounds that are produced by the organism, describe their structure, and run assays to determine biological actions.
From Land to Sea: Researching Marine Compounds
More recently, research has branched out to include an area previously untapped area: the ocean. The ocean is a vast untapped reservoir of biological and chemical diversity. Each milliliter of seawater collected near the surface of the ocean contains about one million microbes. The same amount of water collected from the ocean floor contains about one billion microbes. And this is only considering microbes! The ocean is home to a variety of life forms including fish, algae, snails, sponges, reefs, bacteria, and much, much more. Medicinal chemists have only just begun to explore the potential of this amazing source of natural compounds.
Many of the agents discovered so far from marine sources are under investigation for anti-cancer activity. This is primarily because the National Cancer Institute finances much of the research in this field. However, the National Institute of Health recently set up grants for the purpose of screening marine compounds against a much larger assay of potential uses, including antibiotic, antimalarial, anti-HIV, and much, much more. This is an exciting prospect in the quest for new pharmaceutical agents to treat a variety of conditions.
The relatively new practice of using the ocean to procure specimens has provided researchers with a whole new group of organisms with which to isolate compounds. Because these compounds are so different from terrestrial sources, new techniques had to be developed in order to isolate and describe them.
Challenges of Working With Marine Natural Products
One major problem working with chemicals produced in nature is the available supply. Collecting enough material for research is often challenging. Often the only practical solution is large-scale collection and extraction of the organism that produces the compound of interest.
An alternative to large-scale collection can be to study the predator-prey relationships. One example of this is in the mollusk/macroalga relationship. Collecting mollusks rather than macroalga can increase yield by a factor of 10,000. This is because the mollusks eats the macroalga and concentrates the compounds produced by the macroalga. While each macroalga may only produce a small amount of the material in question, the mollusks will consume many macroalga. As it continues to devour more and more macroalga, the mollusk will naturally begin to accumulate the compounds of the macroalga. This is why the compound of interest may be found in much greater quantities if the researcher concentrates on extracting from the predator rather than the prey.
Another unique challenge in marine natural products is determining the true producer of a particular compound. Whenever bulk extractions are run on large samples, there is a possibility that the compounds isolated may come from multiple sources. For example, when running extractions on large batches of sponges, there is a high probability that the batch will also contain at least some cyanobacteria. The challenge for the researcher is to determine which compounds are produced by the sponge and which ones are produced by the bacteria. Thankfully the products of cyanobacteria are often distinctive enough chemically to allow the researcher to determine the true producer of the compound without the need for further testing.
The field of marine natural products chemistry is one of the most promising in the continued search for new pharmaceutical agents. Interested parties are encouraged to learn more about this exciting field from trade journals such as The Journal of Natural Products or Drug Discovery Today, by visiting marine ecology exhibits, or by contacting research groups in this field such as The Smithsonian Martine Research Station or Harbor Branch Oceanographic Institute.