Translational Biodiscovery: Identifying and Develop-ing New Drugs from Nature

Emerging challenges within the current drug discovery para-digm are prompting renewed interest in secondary metabolites as an attractive source of novel, structurally diverse small mol-ecules that have been evolutionarily ‘pre-selected’ for bioactiv-ity. With the recent validation of zebrafish as a biomedically relevant model for functional genomics and in vivo drug dis-covery, the zebrafish bioassay-guided identification of natural products is an attractive strategy to generate new lead com-pounds in a number of indication areas. We have recently de-veloped a number of in vivo, microgram-scale, high-throughput bioassays based on zebrafish embryos and larvae for the sys-tematic identification and pharmacological characterization of bioactive natural products. Zebrafish offer the ability to rapidly evaluate – at a very early stage in the drug discovery process – not only the therapeutic potential of natural products, but also their potential hepato-, cardio-, and neurotoxicities. Due to the requirement for only microgram quantities of compounds to be tested, in vivo assays based on zebrafish are useful not only for bioassay-guided isolation, but also for the subsequent derivati-zation of bioactive natural products prioritized for further de-velopment as drug discovery leads.