ISOLATION OF ANTIPROLIFERATIVE COMPOUNDS FROM CENTAUREA JACEA L.

Abstract

Antiproliferative screening of 53 Asteraceae species against human tumour cell lines demonstrated a high cell proliferation inhibitory activity of the Centaurea species native to Middle and Eastern Europe. The highest activity was recorded for C. jacea, whose chloroform extract, prepared from different plant parts, significantly inhibited the growth of HeLa (57-86 %), MCF7 (44-64 %) and A431 (43-69 %) cells in 10 µg/ml concentrations. This species is a perennial herb occurring widespread in Europe. Its anti-tumour constituents have not been investigated earlier. Previous studies revealed the presence of flavones, flavonols, sesquiterpenes and cinnamic alcohol glucosides. The aim of the present work was the isolation and identification of the antiproliferative compounds from the aerial parts of C. jacea using bioactivity guided fractionations. The chloroform extract was chromatographed by CC on silica gel and polyamide, and further separated by CPC, PLC and RP-HPLC, to yield 10 pure compounds. Structure determinations were carried out by means of UV, MS and NMR spectroscopy and the comparison of the spectral data with literature values. The results allowed the identification of the flavonoid apigenin, axillarin, centaureidin, cirsiliol and isokaempferide, the sesquiterpene 4’-acetylcnicin, one new dibenzylbutyrolactone-type lignane, and three aliphatic glucose diesters, including the new natural product 1-beta-isobutanoyl-2-angeloylglucose. All compounds were isolated for the first time from this species. The isolated compounds were evaluated for their tumour cell inhibitory activity on HeLa, MCF7 and A431 cells and it was found that besides the extremely active centaureidin (IC50 0.0819–0.3540 microM), cirsiliol, isokaempferide, apigenin and 4’-acetylcnicin also exerted remarkable effects. Acknowledgements: This work was supported by grant OTKA K72771.