Metabolomics of Plant Secondary Compounds: Profiling of Catharanthus Cell Cultures

Abstract

Plants have supplied mankind with potent medication since ancient times and still provide a largely untapped resource for the discovery of novel pharmaceuticals (Verpoorte 1998). Currently only about 10% of higher plants are chemically characterized to some extent. Low molecular weight compounds, usually referred to as ‘secondary metabolites’, exhibit many biological functions such as stress response (Hirai et al. 2004) but for many the exact function remains unknown. Because of their extremely diverse chemical structures and hence their pharmacophoric properties, these natural products constitute an important addition to compound libraries forming the basis for all drug discovery and development efforts (Hostettman and Terreaux 2000). Alkaloids are one of the most studied groups of plant secondary metabolites. Currently about 15,000–16,000 different alkaloids are known (Verpoorte 2000) and they can be further classified into several subclasses according to their chemical structures. In contrast to, e. g. phenolic compounds, which are abundant throughout the whole plant kingdom, alkaloids are often restricted to certain plant families or even certain plant species. The reasonwhy alkaloids have been of such wide interest can be explained by their strong physiological properties leading to their use as, e. g. pharmaceuticals or pesticides. Furthermore, the isolation of alkaloids from plant matrices is relatively simple compared to many other plant compounds. This has allowed scientists to measure and isolate very small amounts of various alkaloids using different chromatographical systems (GC, LC) combined later with spectrometry (e. g. MS, NMR) for their structure elucidations. The importance of plants as a source of new drug molecules can be nicely illustrated by the following figures. During the past 20 years, 28% of new drug entities were either natural products or derived from them as semi-synthetic derivatives and, in addition to that, 24% of the drugs were synthesized after themolecule was first discovered fromnatural resources (Newman et al. 2003). Modern high throughput screenings (HTS) allow enormous numbers of samples to be tested automatically for biological effects using molecular targets (Cordell 2000). There are three strategies usually applied for the discovery of bioactive compounds from plants and all of them have provided promising substances for further testing. The simplest case is the indiscriminate