Zebrafish Bioassay-guided Microfractionation for the Rapid in vivo Identification of Pharmacologically Active Natural Products
DOI:
https://doi.org/10.2533/chimia.2012.229Keywords:
Microflow nmr, Microfractionation, Natural products, Uhplc-tof-ms, ZebrafishAbstract
The rapid acquisition of structural and bioactivity information on natural products (NPs) at the sub- milligram scale is key for performing efficient bioactivity-guided isolations. Zebrafish offer the possibility of rapid in vivo bioactivity analysis of small molecules at the microgram scale – an attractive feature when combined with high-resolution fractionation technologies and analytical methods such as UHPLC-TOF-MS and microflow NMR. Numerous biomedically relevant assays are now available in zebrafish, encompassing most indication areas. Zebrafish also provide the possibility to screen bioactive compounds for potential hepato-, cardio-, and neurotoxicities at a very early stage in the drug discovery process. Here we describe two strategies using zebrafish bioassays for the high-resolution in vivo bioactivity profiling of medicinal plants, using either a one-step or a two-step procedure for active compound isolation directly into 96-well plates. The analysis of the microfractions by microflow NMR in combination with UHPLC-TOF-MS of the extract enables the rapid dereplication of compounds and an estimation of their microgram quantities for zebrafish bioassays. Both the one-step and the two-step isolation procedures enable a rapid estimation of the bioactive potential of NPs directly from crude extracts. In summary, we present an in vivo , microgram-scale NP discovery platform combining zebrafish bioassays with microscale analytics to identify, isolate and evaluate pharmacologically active NPs.Downloads
Published
2012-04-25
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Scientific Articles
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Copyright (c) 2012 Swiss Chemical Society
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How to Cite
[1]
S. Challal, N. Bohni, O. E. Buenafe, C. V. Esguerra, P. A. M. de Witte, J.-L. Wolfender, A. D. Crawford, Chimia 2012, 66, 229, DOI: 10.2533/chimia.2012.229.