California Sea Grant College Program

For more than thirty years, marine natural products chemists have studied sponges, ascidians, and other marine invertebrates because of their ability to produce secondary metabolites with unique chemical structures and potent bioactivities. The remarkable abundance and diversity of bioactive small molecules that have been isolated from marine invertebrates have made these organisms an important source of new drug candidates for human diseases, particularly in the fight against cancer. As a result, there are now a number of marine natural products in clinical or preclinical trials for the treatment of different kinds of cancer.

The objective of this thesis is to describe the isolation and characterization of novel anticancer compounds from marine invertebrates. Each chapter discusses dramatically different types of molecules that have been identified in marine sponges, linked only by the fact that they all demonstrate activity on a cancer or cancer-related assay. The first chapter provides an overview of the various anticancer compounds that have been isolated from marine invertebrates, with particular emphasis on the specific bioactivities demonstrated by each compound. Chapter 2 provides a report of several interesting series of molecules isolated from a single Palauan sponge. The techniques used towards the isolation and structural elucidation of organic compounds, including HPLC, NMR, and mass spectrometry, are presented here before being elaborated upon in subsequent chapters. In chapter 3, a series of compounds are isolated from a Red Sea sponge based on their activity in an assay designed to identify novel cell-cycle inhibitors. In addition to a report of the isolation and structural elucidation of these compounds, this chapter also describes several studies aimed at further characterizing their bioactivity. Chapter 4 presents two completely novel compounds isolated from a new deep-water sponge. Several interesting techniques were employed to develop a model of the relative stereochemistry of neighboring chiral centers within each molecule. Ultimately, a story is told of the challenges and solutions involved in purifying and characterizing marine invertebrate natural products.