Natural products in high throughput screening: Automated high-quality sample preparation

At present, compound libraries from combinatorial chemistry are the major s ource for high throughput screening (HTS) programs in drug discovery. On th e other hand, nature has been proven to be an outstanding source for new an d innovative drugs. Secondary metabolites from plants, animals, and microor ganisms show a striking structural diversity that supplements chemically sy nthesized compounds or libraries in drug discovery programs. Unfortunately, extracts from natural sources are usually complex mixtures of compounds, o ften generated in time-consuming and, for the most part, manual processes. Because quality and quantity of the provided samples play a pivotal role in the success of HTS programs, this poses serious problems. In order to make samples of natural origin competitive with synthetic compound libraries, w e devised a novel, automated sample preparation procedure based on solid-ph ase extraction (SPE), By making use of modified Zymark (Hopkinton, MA) Rapi dTrace(R) SPE workstations, we developed an easy-to-handle and effective fr actionation method that generates high-quality samples from natural origin, fulfilling the requirements for an integration in high throughput drug dis covery programs.