Analytical tools for the detection and characterization of biologically active compounds from nature

Nature has been recognized as a rich source of medicinal compounds for hundreds to thousands of years. Today, a vast range of drugs, which represent the cornerstones of modern pharmaceutical care, are either natural products or have been derived from them. Though providing high chemical diversity, the implementation of natural product research in modern High Throughput Screening (HTS) programs has decreased considerably during the last decade. Instead, seemingly more cost-effective and HTS compatible approaches such as combinatorial chemistry have been explored in an effort to increase the number and diversity of chemical entities. However, pharmaceutical companies are facing enormous challenges as advances in human genome description have led to an increasing number of new molecular drug targets and intensified the need for new, additional molecular diversity as a source of novel drug molecules. Natural products still offer an attractive route to alternative chemical diversities and possess a proven track record in pharmaceutical medications. Consequently, a high demand exists for novel and highly efficient screening technologies, which enable successful incorporation of natural products in drug discovery programs. Over recent years several techniques have been developed, which interfaced continuous-flow biochemical detection with a range of analytical instruments, such as LC, DAD, UV and MS. The combination of analytical technologies and continuous-flow biochemical detection has enabled biological and chemical evaluation of bioactive molecules within a single analysis and profoundly reduces the time required for compound characterization. Recent advances in this field as well as the application of continuous-flow biochemical detection for the screening of complex mixtures, such as natural product extracts, are reviewed in this paper.