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:	Alexander D Crawford, Sandra Liekens, Appolinary R Kamuhabwa, Jan Maes, Sebastian Munck, Roger Busson, Jef Rozenski, Camila V Esguerra, Peter A M de Witte
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/71b687a0d6fe430fac940e3f9ada55c7
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spelling	oai:doaj.org-article:71b687a0d6fe430fac940e3f9ada55c72021-11-18T06:58:37ZZebrafish bioassay-guided natural product discovery: isolation of angiogenesis inhibitors from East African medicinal plants.1932-620310.1371/journal.pone.0014694https://doaj.org/article/71b687a0d6fe430fac940e3f9ada55c72011-02-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21379387/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Natural 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.Alexander D CrawfordSandra LiekensAppolinary R KamuhabwaJan MaesSebastian MunckRoger BussonJef RozenskiCamila V EsguerraPeter A M de WittePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 2, p e14694 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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.
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.
format	article
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
title	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_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_sort	zebrafish bioassay-guided natural product discovery: isolation of angiogenesis inhibitors from east african medicinal plants.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/71b687a0d6fe430fac940e3f9ada55c7
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Zebrafish bioassay-guided natural product discovery: isolation of angiogenesis inhibitors from East African medicinal plants.

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