zebrafish bioassay-guided natural product discovery isolation of angiogenesis inhibitors from east african medicinal plants获得斑马鱼血管生成抑制剂的天然产物的发现隔离从东非洲药用植物.pdfVIP

Zebrafish Bioassay-Guided Natural Product Discovery: Isolation of Angiogenesis Inhibitors from East African Medicinal Plants 1 2,3 4 1 5 Alexander D. Crawford *, Sandra Liekens , Appolinary R. Kamuhabwa , Jan Maes , Sebastian Munck , 1,2 1,2 1 1 Roger Busson , Jef Rozenski , Camila V. Esguerra , Peter A. M. de Witte * 1 Department of Pharmaceutical Sciences, University of Leuven, Leuven, Belgium, 2 Rega Institute for Medical Research, University of Leuven, Leuven, Belgium, 3 Department of Microbiology and Immunology, University of Leuven, Leuven, Belgium, 4 Department of Pharmacognosy, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania, 5 Department of Human Genetics, Flanders Interuniversity Institute of Biotechnology, University of Leuven, Leuven, Belgium Abstract Natural products represent a significant reservoir of unexplored chemical diversity for early-stage drug discovery. The identification of lead compounds of natural origin would benefit from therapeutically relevant bioassays capable of facilitating the isolation of bioactive molecules from multi-constituent extracts. Towards this end, we developed an in vivo bioassay-guided isolation approach for natural product discovery that combines bioactivity screening in zebrafish embryos with rapid fractionation by analytical thin-layer chromatography (TLC) and initial structural elucidation by high-resolution electrospray mass spectrometry (HRESIMS). Bioactivity screening of East African medicinal plant extracts using fli-1:EGFP tra