School of Chinese Medicine
Folding fan mode counter-current chromatography offers fast blind screening for drug discovery. Case study: Finding anti-enterovirus 71 agents from Anemarrhena asphodeloides
© 2014 Elsevier B.V.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.
A. asphodeloides, Bioassay-guided counter-current chromatography, Enterovirus 71, Folding fan mode, Structure-activity relationship
Source Publication Title
Journal of Chromatography A
Link to Publisher's Edition
Liu, M., Tao, L., Chau, S., Wu, R., Zhang, H., Yang, Y., Yang, D., Bian, Z., Lu, A., Han, Q., & Xu, H. (2014). Folding fan mode counter-current chromatography offers fast blind screening for drug discovery. Case study: Finding anti-enterovirus 71 agents from Anemarrhena asphodeloides. Journal of Chromatography A, 1368, 116-124. https://doi.org/10.1016/j.chroma.2014.09.064