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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Integration of Microfractionation, qNMR and Zebrafish Screening for the In Vivo Bioassay-Guided Isolation and Quantitative Bioactivity Analysis of Natural Products
PLoS ONE, Volume 8, No. 5, Article e64006, Year 2013
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Description
Natural products (NPs) are an attractive source of chemical diversity for small-molecule drug discovery. Several challenges nevertheless persist with respect to NP discovery, including the time and effort required for bioassay-guided isolation of bioactive NPs, and the limited biomedical relevance to date of in vitro bioassays used in this context. With regard to bioassays, zebrafish have recently emerged as an effective model system for chemical biology, allowing in vivo high-content screens that are compatible with microgram amounts of compound. For the deconvolution of the complex extracts into their individual constituents, recent progress has been achieved on several fronts as analytical techniques now enable the rapid microfractionation of extracts, and microflow NMR methods have developed to the point of allowing the identification of microgram amounts of NPs. Here we combine advanced analytical methods with high-content screening in zebrafish to create an integrated platform for microgram-scale, in vivo NP discovery. We use this platform for the bioassay-guided fractionation of an East African medicinal plant, Rhynchosia viscosa, resulting in the identification of both known and novel isoflavone derivatives with anti-angiogenic and anti-inflammatory activity. Quantitative microflow NMR is used both to determine the structure of bioactive compounds and to quantify them for direct dose-response experiments at the microgram scale. The key advantages of this approach are (1) the microgram scale at which both biological and analytical experiments can be performed, (2) the speed and the rationality of the bioassay-guided fractionation - generic for NP extracts of diverse origin - that requires only limited sample-specific optimization and (3) the use of microflow NMR for quantification, enabling the identification and dose-response experiments with only tens of micrograms of each compound. This study demonstrates that a complete in vivo bioassay-guided fractionation can be performed with only 20 mg of NP extract within a few days. © 2013 Bohni et al.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC3660303/bin/pone.0064006.s001.pdf
https://efashare.b-cdn.net/share/pmc/articles/PMC3660303/bin/pone.0064006.s002.doc
https://efashare.b-cdn.net/share/pmc/articles/PMC3660303/bin/pone.0064006.s003.doc
Authors & Co-Authors
Bohni, Nadine
Switzerland, Geneva
Université de Genève
Cordero-Maldonado, María Lorena
Belgium, Leuven
Departement Farmaceutische en Farmacologische Wetenschappen
Ecuador, Cuenca
University of Cuenca
Maes, Jan
Belgium, Leuven
Departement Farmaceutische en Farmacologische Wetenschappen
Siverio-Mota, Dany
Belgium, Leuven
Departement Farmaceutische en Farmacologische Wetenschappen
Marcourt, Laurence
Switzerland, Geneva
Université de Genève
Munck, Sebastian
Belgium, Leuven
Ku Leuven
Kamuhabwa, Appolinary A.R.
Tanzania, Dar es Salaam
Muhimbili University of Health and Allied Sciences
Moshi, Mainen Julius
Tanzania, Dar es Salaam
Muhimbili University of Health and Allied Sciences
Esguerra, Camila V.
Belgium, Leuven
Departement Farmaceutische en Farmacologische Wetenschappen
De Witte, Peter A.M.
Belgium, Leuven
Departement Farmaceutische en Farmacologische Wetenschappen
Crawford, Alexander D.
Belgium, Leuven
Departement Farmaceutische en Farmacologische Wetenschappen
Wolfender, Jean Luc
Switzerland, Geneva
Université de Genève
Statistics
Citations: 55
Authors: 12
Affiliations: 5
Identifiers
Doi:
10.1371/journal.pone.0064006
e-ISSN:
19326203
Study Approach
Quantitative