Zebrafish bioassay-guided natural product discovery: isolation of angiogenesis inhibitors from East African medicinal plants.
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-con...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2011-02-01
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| Series: | PLoS ONE |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21379387/pdf/?tool=EBI |
| _version_ | 1818402850845229056 |
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| author | Alexander D Crawford Sandra Liekens Appolinary R Kamuhabwa Jan Maes Sebastian Munck Roger Busson Jef Rozenski Camila V Esguerra Peter A M de Witte |
| author_facet | Alexander D Crawford Sandra Liekens Appolinary R Kamuhabwa Jan Maes Sebastian Munck Roger Busson Jef Rozenski Camila V Esguerra Peter A M de Witte |
| author_sort | Alexander D Crawford |
| collection | DOAJ |
| description | 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 transgenic zebrafish embryos identified Oxygonum sinuatum and Plectranthus barbatus as inhibiting vascular development. Zebrafish bioassay-guided fractionation identified the active components of these plants as emodin, an inhibitor of the protein kinase CK2, and coleon A lactone, a rare abietane diterpenoid with no previously described bioactivity. Both emodin and coleon A lactone inhibited mammalian endothelial cell proliferation, migration, and tube formation in vitro, as well as angiogenesis in the chick chorioallantoic membrane (CAM) assay. These results suggest that the combination of zebrafish bioassays with analytical chromatography methods is an effective strategy for the rapid identification of bioactive natural products. |
| first_indexed | 2024-12-14T08:14:55Z |
| format | Article |
| id | doaj.art-71b687a0d6fe430fac940e3f9ada55c7 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-14T08:14:55Z |
| publishDate | 2011-02-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-71b687a0d6fe430fac940e3f9ada55c72022-12-21T23:09:57ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-02-0162e1469410.1371/journal.pone.0014694Zebrafish bioassay-guided natural product discovery: isolation of angiogenesis inhibitors from East African medicinal plants.Alexander D CrawfordSandra LiekensAppolinary R KamuhabwaJan MaesSebastian MunckRoger BussonJef RozenskiCamila V EsguerraPeter A M de WitteNatural 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 transgenic zebrafish embryos identified Oxygonum sinuatum and Plectranthus barbatus as inhibiting vascular development. Zebrafish bioassay-guided fractionation identified the active components of these plants as emodin, an inhibitor of the protein kinase CK2, and coleon A lactone, a rare abietane diterpenoid with no previously described bioactivity. Both emodin and coleon A lactone inhibited mammalian endothelial cell proliferation, migration, and tube formation in vitro, as well as angiogenesis in the chick chorioallantoic membrane (CAM) assay. These results suggest that the combination of zebrafish bioassays with analytical chromatography methods is an effective strategy for the rapid identification of bioactive natural products.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21379387/pdf/?tool=EBI |
| spellingShingle | Alexander D Crawford Sandra Liekens Appolinary R Kamuhabwa Jan Maes Sebastian Munck Roger Busson Jef Rozenski Camila V Esguerra Peter A M de Witte Zebrafish bioassay-guided natural product discovery: isolation of angiogenesis inhibitors from East African medicinal plants. PLoS ONE |
| title | Zebrafish bioassay-guided natural product discovery: isolation of angiogenesis inhibitors from East African medicinal plants. |
| title_full | Zebrafish bioassay-guided natural product discovery: isolation of angiogenesis inhibitors from East African medicinal plants. |
| title_fullStr | Zebrafish bioassay-guided natural product discovery: isolation of angiogenesis inhibitors from East African medicinal plants. |
| title_full_unstemmed | Zebrafish bioassay-guided natural product discovery: isolation of angiogenesis inhibitors from East African medicinal plants. |
| title_short | Zebrafish bioassay-guided natural product discovery: isolation of angiogenesis inhibitors from East African medicinal plants. |
| title_sort | zebrafish bioassay guided natural product discovery isolation of angiogenesis inhibitors from east african medicinal plants |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21379387/pdf/?tool=EBI |
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