Macromarines

Macromarines A Selective Account of the Potential of Marine Sponges, Molluscs, Soft Corals and Tunicates as a Source of Therapeutically Important Molecular Structures... 

This chapter reviews a selection of marine invertebrates and the compounds isolated from them which have therapeutic potential. The major phyla of macromarines discussed include the marine Porifera, Mollusca, the soft corals of Cnidaria and the tunicates which belong to the sub-phylum of Urochordates. The isolation, synthesis, preclinical data and structure-activity relationships (SARs) are discussed for a selection of pharmacologically important chemical structures for each of the four groups. 

Figure 6.3 Evolution of macromarines (adapted from Muller 2003). Modem Phyla are in bold.

A number of historically significant marine natural products have established macromarines as a valuable source of physiologically active molecular scaffolds. In addition, many of the compounds illustrated in this work are currently in clinical development. Unfortunately, the journey from initial isolation to clinical development has ended for a number of notable compounds. Among the list found in Table 6.1 are leads obtained from the macromarines such as sponges, tunicates and molluscs. Although synthetic derivatives often attempt... 

One of the biggest issues hindering the utilisation of macromarine compounds as drugs is that of supply. Total synthesis, partial synthesis and the semi-synthesis of natural products may reduce the demand pressure during commercial development however, the complexity of natural products extends the timeline for the realistic production of material needed for clinical testing. Sensible mariculture techniques will undoubtedly help to preserve the natural sources for these compounds while also allowing for testing to continue. 

The supply problem may be alleviated if the true producers of these biologically active compounds could be identified. Once this can be established, the next step is to isolate the gene clusters responsible for these novel structural scaffolds. Combined with biosynthetic engineering, a solution to the supply problem could be readily at hand allowing a greater number of macromarine agents through the pharmaceutical development pipeline. 

Plants, microorganisms and, to a lesser extent, macromarines have been the main sources of natural product based drugs (produced as secondary metabolites). Reviews of these traditional sources of naturally occurring chemical compounds are found in Chapters 5-7, together with hints and suggestions as to how these sources may be better utilised to continue supplying new drug leads in the future. 

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