An Update on the Biomedical Prospects of Marine‐derived Small Molecules with Fascinating Atom and Stereochemical Diversity

Abstract

In this chapter we discuss a selection of structurally diverse marine-derived small molecules (MDSMs) with potent and/or specific bioactivity and analyze their biomedical applications. The compounds included have been isolated either from marine macroorganisms, including sponges, ascidians (tunicates), bryozoans, and molluscs, or from microorganisms, such as bacteria and fungi. Our inquiry begins with a look back in time at a selection of important marine natural products, with particular focus on compounds in the clinical pipeline. The chapter continues with an analysis of a biosynthetically diverse assortment of 22 MDSMs and their structural elements of atom and stereochemical diversity. Entries have been divided into five biosynthetic classes: terpene, polyketide, alkaloid, depsipeptide, and polyketide-peptide. Enormous structural variety is represented by the marine natural products treated herein. The compounds selected can be considered to represent case examples of significant biomolecules with positivity and, in some cases, potent bioactivity accompanied by an unusual mechanism of action. Overview of known compounds, highlighting molecules of significanceThe ocean covers more than 70% of the earth's surface and is home to exceptional biodiversity: more than one million marine species and an estimated one billion different kinds of marine microbe (Census of Marine Life Press Release 2010). We and others firmly believe that MDSMs represent a continuing resource for tools important in cell biology research and in the design of the next-generation leads for drug discovery and development. The record to date firmly illustrates that the structures of natural products continue to be invaluable in expanding pharmacophore structural space. For example, Newman and Cragg recently provided a detailed analysis of the last 30 years of natural products in drug discovery, wherein they contended that, "Nature's 'treasure trove of small molecules' remains to be explored, particularly from the marine and microbial environments" (Newman & Cragg 2012).

Xenicane Natural Products: Biological Activity and Total Synthesis

“…Biological properties ranging from cytotoxic, antiproliferative, antibacterial, antifungal, algicidal to many other effects have been observed for marine secondary metabolites (vide infra). When compared to their terrestrial counterparts, a higher incidence of significant bioactivity has been noted for marine natural products and this is often associated with a high degree of chemical novelty; i. e. many newly discovered bioactive marine natural products display novel types of chemical structures [11,15]. While the ocean harbors many creatures we have not been closely interacting with for ages [13], eukaryotic physiology evolved in our early marine ancestors and is highly conserved [8].…”