Document Type

Journal Article

Department/Unit

School of Chinese Medicine

Title

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

Language

English

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.

Keywords

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

Publication Date

11-2014

Source Publication Title

Journal of Chromatography A

Volume

1368

Start Page

116

End Page

124

Publisher

Elsevier

Peer Reviewed

1

Funder

This work was supported by the National Natural Science Foun-dation of China (Grant No. 81303289), the Major ApplicationDevelopment Project of Chongqing (cstc2014yykfc10002), the Sci-ence Foundation for the Excellent Youth Scholars of Shanghai (No.ZZszy13059), and Hong Kong Baptist University (FRG2/13-14/026).We thank Dr. Long Song from the School of Pharmacy, ShanghaiUniversity of Traditional Chinese Medicine for identification of A.asphodeloides; and Professor Hanzhong Wang from the WuhanInstitute of Virology, Chinese Academy of Sciences, for providingthe BrCr strain of EV71.

DOI

10.1016/j.chroma.2014.09.064

ISSN (print)

00219673

ISSN (electronic)

18733778

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