The marine environment has proven to be a very rich source of extremely potent compounds that have demonstrated significant activities in antitumor, antiinflammatory, analgesia, immunomodulation, allergy, and anti-viral assays. Although the case can and has been made that the nucleosides such as Ara-A and Ara-C are derived from knowledge gained from investigations of bioactive marine nucleosides, no drug directly from marine sources (whether isolated or by total synthesis) has yet made it to the commercial sector in any disease. However, as shown in this review, there are now significant numbers of very interesting molecules that have come from marine sources, or have been synthesized as a result of knowledge gained from a prototypical compound, that are either in or approaching Phase II/III clinical trials in cancer, analgesia, allergy, and cognitive diseases. A substantial number of other potential agents are following in their wake in preclinical trials in these and in other diseases.

Marine Natural Products and Related Compounds in Clinical and Advanced Preclinical Trials

Phospholipase A2: function and pharmacological regulation.

The Ocean, which is called the ‘mother of origin of life’, is also the source of structurally unique natural products that are mainly accumulated in living organisms. Several of these compounds show pharmacological activities and are helpful for the invention and discovery of bioactive compounds, primarily for deadly diseases like cancer, acquired immuno-deficiency syndrome (AIDS), arthritis, etc., while other compounds have been developed as analgesics or to treat inflammation, etc. The lifesaving drugs are mainly found abundantly in microorganisms, algae and invertebrates, while they are scarce in vertebrates. Modern technologies have opened vast areas of research for the extraction of biomedical compounds from oceans and seas.

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Biomedical Compounds from Marine organisms

Phospholipase A2 enzymes: regulation and inhibition

Marine natural products, the secondary or nonprimary metabolites produced by organisms that live in the sea, have received increasing attention from chemists and pharmacologists during the last two decades. Interest on the part of chemists has been twofold: natural products chemists have probed marine organisms as sources of new and unusual organic molecules, while synthetic chemists have followed by targeting these novel structures for development of new analogs and new synthetic methodologies and strategies (Albizati et al., 1990). The rationale for investigating the chemistry of marine organisms has changed over the past several decades. Early investigations were largely of a “phytochemical” nature, reporting detailed metabolite profiles similar to those reported for terrestrial plants in previous decades. However, analogous to investigations of terrestrial plants, more recent studies of marine organisms have focused on their potential applications, particularly to the treatment of human disease and control of agricultural pests (Fautin, 1988). Pharmacological evaluations of marine natural products have likewise undergone an evolution over the past two decades: beginning with the early investigations of toxins, followed by studies of cytotoxic and antitumor activity, to the present day, where a myriad of activities based on whole-animal models and receptor-binding assays are being pursued. The intent of this chapter is to look back at the evolution of biomedically oriented natural product studies of marine organisms, to chronicle the key developments, discoveries, and advances in the level of sophistication that have fueled further interest in this field, and finally to look forward at the future biomedical potential of marine natural products.

Ronald B. Langdon

Papers

Some pharmacological observations on marine natural products

Quantal analysis indicates an α-toxin-like block by lophotoxin, a non-ionic marine natural product

Irreversible autonomic actions by lophotoxin suggest utility as a probe for both C6 and C10 nicotinic receptors

An inexpensive frequency-modulated (FM) audio monitor of time-dependent analog parameters.