HPLC-based search for new natural products leads



The discovery platform is used for the identification discovery of new natural product leads. Besides our in-house bioassays, our extract library is screened in other disease/target areas, such as tropical diseases (collaboration with Prof. R. Brun, Swiss Tropical Institute, Basel), GABAA receptor ligands (collaboration with Prof. S. Hering, University of Vienna), angiogenesis (collaboration with Prof. M. Detmar, ETH Zürich), PI 3-kinase inhibitors (collaboration with Prof. M. Wymann, University of Basel). For the identification of leads, we have established and validated screen-specific protocols for the HPLC-based activity profiling.

Valerian (Valeriana officinalis, family Valerianaceae) is a well established sedative, and known to potentiate the effect of γ-aminobutyric acid at GABAA receptors. An activity profile of a valerian extract, obtained with a functional assay in Xenopus oocytes transiently expressing GABAA receptors composed of α2β2γ subunits, shows that the activity peak corresponds to the peak of valerenic acid, whereas acetoxyvalerenic acid is inactive.

Efficient dereplication of known structures or compounds with unfavourable physicochemical properties is carried out by LC-TOF-MS, microprobe NMR, and database searches.

The project is supported by the Swiss National Science Foundation.