Folding fan mode counter-current chromatography offers fast blind screening for drug discovery. Case study: Finding anti-enterovirus 71 agents from Anemarrhena asphodeloides

Mengshun Liu, Ling Tao, Siu Leung Chau, Rong Wu, Hong Zhang, Yifu Yang, Dajian Yang, Zhaoxiang BIAN, Aiping LYU, Simon Q B HAN, Hongxi Xu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

A new application of counter-current chromatography (CCC) in drug discovery, called folding fan mode (FFM), is designed to eliminate the extensive and time-consuming calculation of the partition coefficients of some preset compounds in conventional CCC separation. Careful reading of reports in the literature reveals that, when two-phase solvent systems are listed in a polarity-increasing sequence, the isolates also show a similar trend in polarity. The relationship between the two-phase solvent system and the isolates is like that between the folds and the picture of a folding fan. We can directly select a two-phase solvent system to separate fractions having similar polarity, just as opening a fan reveals a picture. The solvent ratio of two-phase solvent systems can be adjusted according to the polarity and weight ratio of active fractions rather than the partition coefficients. Without preset compounds, FFM-CCC not only requires no measurement of partition coefficients, but also achieves true blind screening. This paper reports the method's first success in drug discovery: six anti-EV71 saponins were found from the mixture (9.13g) of ethanol extract and water extract of Anemarrhena asphodeloides after a total of four CCC separations, using hexan/ethyl acetate/methanol/butanol/water as the model solvent system. Among these saponins, timosaponin B-II displayed a comparable IC50 (4.3±2.1μM) and a 40-fold higher selective index (SI=92.9) than the positive control (IC50=361.7±104.6μM, SI=2.4), ribavirin. The structure-activity relationship (SAR) of these compounds was also studied.

Original languageEnglish
Pages (from-to)116-124
Number of pages9
JournalJournal of Chromatography A
Volume1368
DOIs
Publication statusPublished - 14 Nov 2014

Scopus Subject Areas

  • Analytical Chemistry
  • Biochemistry
  • Organic Chemistry

User-Defined Keywords

  • A. asphodeloides
  • Bioassay-guided counter-current chromatography
  • Enterovirus 71
  • Folding fan mode
  • Structure-activity relationship

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