| Autor: |
Challal S; Université de Genève Quai Ernest-Ansermet, Genève 4, Switzerland., Bohni N, Buenafe OE, Esguerra CV, de Witte PA, Wolfender JL, Crawford AD |
| Jazyk: |
angličtina |
| Zdroj: |
Chimia [Chimia (Aarau)] 2012; Vol. 66 (4), pp. 229-32. |
| DOI: |
10.2533/chimia.2012.229 |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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