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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...

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Autores principales: Crawford, Alexander D., Liekens, Sandra, Kamuhabwa, Appolinary R., Maes, Jan, Munck, Sebastian, Busson, Roger, Rozenski, Jef, Esguerra, Camila V., de Witte, Peter A. M.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3040759/
https://www.ncbi.nlm.nih.gov/pubmed/21379387
http://dx.doi.org/10.1371/journal.pone.0014694
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author Crawford, Alexander D.
Liekens, Sandra
Kamuhabwa, Appolinary R.
Maes, Jan
Munck, Sebastian
Busson, Roger
Rozenski, Jef
Esguerra, Camila V.
de Witte, Peter A. M.
author_facet Crawford, Alexander D.
Liekens, Sandra
Kamuhabwa, Appolinary R.
Maes, Jan
Munck, Sebastian
Busson, Roger
Rozenski, Jef
Esguerra, Camila V.
de Witte, Peter A. M.
author_sort Crawford, Alexander D.
collection PubMed
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.
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spelling pubmed-30407592011-03-04 Zebrafish Bioassay-Guided Natural Product Discovery: Isolation of Angiogenesis Inhibitors from East African Medicinal Plants Crawford, Alexander D. Liekens, Sandra Kamuhabwa, Appolinary R. Maes, Jan Munck, Sebastian Busson, Roger Rozenski, Jef Esguerra, Camila V. de Witte, Peter A. M. PLoS One Research Article 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. Public Library of Science 2011-02-17 /pmc/articles/PMC3040759/ /pubmed/21379387 http://dx.doi.org/10.1371/journal.pone.0014694 Text en Crawford et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Crawford, Alexander D.
Liekens, Sandra
Kamuhabwa, Appolinary R.
Maes, Jan
Munck, Sebastian
Busson, Roger
Rozenski, Jef
Esguerra, Camila V.
de Witte, Peter A. M.
Zebrafish Bioassay-Guided Natural Product Discovery: Isolation of Angiogenesis Inhibitors from East African Medicinal Plants
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
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3040759/
https://www.ncbi.nlm.nih.gov/pubmed/21379387
http://dx.doi.org/10.1371/journal.pone.0014694
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