Targeted Approaches in Natural Product Lead Discovery

Natural products still constitute a prolific source of lead compounds for the development of novel drugs. Due to their unmatched structural diversity they represent an indispensable complement to synthetic compound collections and virtual libraries. However, the tremendous changes which have taken place in the drug discovery process over the last decade have put completely new requirements on natural product research. The classical bioactivity-guided approach no more matches the timelines and the workflow of modern drug discovery. More targeted approaches are needed in order to identify promising candidate molecules at an early stage and to accelerate the follow-up process. We describe here our strategy for tracking bioactive components in complex mixtures and discuss the potential of accurate mass measurements for natural product identification and the impact of mass controlled preparative HPLC on the isolation process of bioactive compounds.