Rapid screening of neuraminidase inhibitors with the benzoic acid skeleton from Paeonia suffruticosa Andrews by solid-phase extraction with an enzyme activity switch combined with mass spectrometry analysis

Abstract

It is meaningful for drug discovery to discover lead compounds with specific skeletons from medicinal herbs. Screening bioactive compounds with specific skeletons by a simple and rapid strategy is still a challenging task. Solid-phase extraction (SPE) is a simple and time-saving technique in the laboratory and is often used in the concentration of natural products. It is attractive to apply the SPE in the screening of bioactive compounds with specific skeletons. To achieve this goal, SPE with an enzyme activity (EA) switch combined with mass spectrometry analysis was first proposed. The screening of benzoic acid-derived neuraminidase (NA) inhibitors from the root cortex of Paeonia suffruticosa Andrews (CPSA) was used as an example. The NA and crude extract of CPSA were incubated to form a sample solution. Subsequently, the sample was separated, detected, and collected by the SPE with an EA switch. When the detected values reduced significantly, the EA switch was triggered, and the collection was stopped. The collected eluents were treated for LC-MS/MS analysis. Finally, combining diagnostic ions and mass spectrometry data, two benzoic acid NA inhibitors were successfully screened from CPSA. In this study, the separation, detection, and collection were performed on one instrument system. Compared with the traditional isolation strategy, this strategy with the simpler operation and higher experimental efficiency could be an effective tool for the rapid screening of lead compounds with specific skeletons.

Keywords: Enzyme activity switch; Fragment pathway; Solid-phase extraction; Specific skeleton.