生物测定
药物发现
天然产物
分馏
生物活性
计算生物学
化学分馏
生物
组合化学
化学
色谱法
生物化学
体外
遗传学
作者
Louis‐Félix Nothias,Mélissa Nothias-Esposito,Ricardo R. da Silva,Mingxun Wang,Ivan Protsyuk,Zheng Zhang,Abi Sarvepalli,Pieter Leyssen,David Touboul,Jean Costa,Julien Paolini,Theodore Alexandrov,Marc Litaudon,Pieter C. Dorrestein
标识
DOI:10.1021/acs.jnatprod.7b00737
摘要
It is a common problem in natural product therapeutic lead discovery programs that despite good bioassay results in the initial extract, the active compound(s) may not be isolated during subsequent bioassay-guided purification. Herein, we present the concept of bioactive molecular networking to find candidate active molecules directly from fractionated bioactive extracts. By employing tandem mass spectrometry, it is possible to accelerate the dereplication of molecules using molecular networking prior to subsequent isolation of the compounds, and it is also possible to expose potentially bioactive molecules using bioactivity score prediction. Indeed, bioactivity score prediction can be calculated with the relative abundance of a molecule in fractions and the bioactivity level of each fraction. For that reason, we have developed a bioinformatic workflow able to map bioactivity score in molecular networks and applied it for discovery of antiviral compounds from a previously investigated extract of Euphorbia dendroides where the bioactive candidate molecules were not discovered following a classical bioassay-guided fractionation procedure. It can be expected that this approach will be implemented as a systematic strategy, not only in current and future bioactive lead discovery from natural extract collections but also for the reinvestigation of the untapped reservoir of bioactive analogues in previous bioassay-guided fractionation efforts.
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