Antiproliferative sesquiterpenes and flavonoids from Anthemis ruthenica L.

As a part of a continuing search aimed at the discovery of novel compounds with antiproliferative activity from Hungarian plants belonging to the Asteraceae family, it was found that the herbs of Anthemis ruthenica M. Bieb. exert high antiproliferative activity against cervix adenocarcinoma (HeLa), breast adenocarcinoma (MCF7) and skin epidermoid carcinoma (A431) cells using the MTT assay [1]. Previous publications dealing with this species reported only the composition of the volatile oil obtained from the plant [2].

The present paper reports the isolation of a new eudesmanolide sesquiterpene, sivasinolide-6-O-angelate, and the known compounds chrysanin, tanacin, eupatolide, centauridin, and centaureidin from the aerial parts of A. ruthenica. The compounds were isolated using bioactivity guided fractionation from the CHCl₃ extract of the herb, which displayed high tumor cell proliferation inhibitory activity. The structures were determined by UV, HRESI-MS, high-field 1D and 2D NMR spectral analyses, affording complete ¹H and ¹³C NMR assignments for all isolated compounds. The antiproliferative activity of the sesquiterpenes and flavonoids was assessed against three cell lines mentioned above, and found that besides the extremely active centaureidin, all isolated compounds exert high or moderate antitumor effect. The germacranolide taxillin and 3β-hydroxycostunolide displayed higher activity, while the eudesmanolides sivasinolide-6-O-angelate and chrysanin were marginally active.

Acknowledgements: Financial support by the Hungarian Research Fund Agency (OTKA grant K72771) is gratefully acknowledged. The authors thank Dr. Pál Szabó (Chemical Research Centre, Hungarian Academy of Sciences, Budapest) for the mass spectral measurements.

References: [1] Réthy, B. et al. (2007) Phytother. Res. 21:1200–1208.

[2] Vujisic, L. et al. (2006) Flavour Fragr. J. 21:458–461.