Pharmacodynamics BSCI 493 March 2008 Natural drug discovery

Pharmacodynamics BSCI 493 March, 2008

Natural drug discovery is an iterative process, beginning with low cost biochemical and cellular assays, progressing to a final validation using expensive animal models, and finally clinical trials.

How Bioassays Are Used • Detecting the presence of the bioactive compound in a crude extract • Guiding fractionation to obtain pure bioactive compound • Biological characterization of isolated compound

Other relevant issues • Prescreening your starting material using ethnobotanical approaches • Efficient strategies for handling massive amounts of bioassay data • Nanotechnology – high throughput screening • Chemical diversity – natural products provide unique structural motifs • Molecular biology – new targets for screening small molecule libraries

Single target bioassay • • Primary screen (increase hits) Test of isolated enzyme, receptor binding High degree of specificity Observed effect can be assigned to a specific mechanism • Know mechanistic class of compounds with improved biopharmaceutical profile • Easy to use in HTS

Multi-target bioassay • Secondary screen (winnow down potential drug candidates) • Test on whole animal, isolated organ, or intact cell • Not easily assigned to a specific mode of action • Interaction between bioactive compound assay takes place simultaneously on many levels • Cell membrane • Secondary messengers • Ion channels • Identifies new targets and/or biochemical novelty