Integration of micro-fractionation, high-performance liquid chromatography-ultraviolet detector-charged aerosol detector-mass spectrometry analysis and cellular dynamic mass redistribution assay to accelerate alkaloid drug discovery

	Integration of micro-fractionation, high-performance liquid chromatography-ultraviolet detector-charged aerosol detector-mass spectrometry analysis and cellular dynamic mass redistribution assay to accelerate alkaloid drug discovery
	Wang, Rong; Liu, Yanfang; Zhou, Han; Chen, Yue; Wang, Jixia; Zhang, Xiuli; Yu, Ruitao; Liang, Xinmiao
刊名	JOURNAL OF CHROMATOGRAPHY A
	2020
卷号	1616
关键词	Alkaloids Drug discovery HPLC micro-fractionation Charged aerosol detector Mass spectrum Cellular dynamic mass redistribution assay
英文摘要	Natural products, including alkaloids, are important resources for new drugs. However, in today's high throughput screening (HTS) environment, natural product drug discovery programs are challenged for their low efficiency. In order to adapt to current HTS models, we here developed a rapid, sample-saving and miniaturized paradigm that seamlessly integrated alkaloid micro-fractionation, quantitative analysis, qualitative analysis and phenotypic screening. In the work, alkaloid samples were analyzed and fractionated on an analytical charged C18 column (150 x 4.6 mm, i.d.), and fraction qualities were determined by a charged aerosol detector (CAD). Fraction activities on dopamine D2 receptor were screened by cellular dynamic mass redistribution (DMR) assay and active fractions were further characterized by high-resolution mass spectrometry (MS). The whole workflow was first validated by mixed standard for accuracy, and then by 300 mu g of Corydalis yanhusuo extract for its feasibility in complex samples. Finally, the method was applied for sample prioritization in four papaveraceae family plants and 21 compounds were predicted to be active, and Corydalis yanhusuo and Corydalis decumbens were determined as promising species for activity tracking. Overall, these results highlighted the feasibility of this miniatured and integrated model in rapid alkaloid screening. Advantages of this workflow were: first, the highly efficient separation method accelerated alkaloid fractionation; second, the analytical and biological test were conducted on the same scale; third, the quantification method ensured accurate screening on microscale; last, the combination of MS analysis and data mining strategy accelerated the decision-making process in the primary screening. (C) 2019 Published by Elsevier B.V.
内容类型	期刊论文
源URL	[http://210.75.249.4/handle/363003/60357]
专题	西北高原生物研究所_中国科学院西北高原生物研究所
推荐引用方式 GB/T 7714	Wang, Rong,Liu, Yanfang,Zhou, Han,et al. Integration of micro-fractionation, high-performance liquid chromatography-ultraviolet detector-charged aerosol detector-mass spectrometry analysis and cellular dynamic mass redistribution assay to accelerate alkaloid drug discovery[J]. JOURNAL OF CHROMATOGRAPHY A,2020,1616.
APA	Wang, Rong.,Liu, Yanfang.,Zhou, Han.,Chen, Yue.,Wang, Jixia.,...&Liang, Xinmiao.(2020).Integration of micro-fractionation, high-performance liquid chromatography-ultraviolet detector-charged aerosol detector-mass spectrometry analysis and cellular dynamic mass redistribution assay to accelerate alkaloid drug discovery.JOURNAL OF CHROMATOGRAPHY A,1616.
MLA	Wang, Rong,et al."Integration of micro-fractionation, high-performance liquid chromatography-ultraviolet detector-charged aerosol detector-mass spectrometry analysis and cellular dynamic mass redistribution assay to accelerate alkaloid drug discovery".JOURNAL OF CHROMATOGRAPHY A 1616(2020).