Novel antileukemic sterol glycosides from Ajuga salicifolia

Akbay P., Gertsch J., Calis I. , Heilmann J., Zerbe O., Sticher O.

HELVETICA CHIMICA ACTA, vol.85, no.7, pp.1930-1942, 2002 (Journal Indexed in SCI) identifier identifier

  • Publication Type: Article / Article
  • Volume: 85 Issue: 7
  • Publication Date: 2002
  • Title of Journal : HELVETICA CHIMICA ACTA
  • Page Numbers: pp.1930-1942


Two novel and three new sterol glycosides were isolated from the MeOH extract of the aerial parts of Ajuga salicifolia (L.) SCHREBER. The structures of the compounds were elucidated as (3R,16S,17S,20R,22S,23S, 24S,25S)-16,23:16,27:22,25-triepoxy-3-(beta-D-glucopyranosyloxy)coprostigmast-7-en-17-ol (1) (3R,16S,17S, 20R,22S,23S,24S,25S)-16,23:16,27:22,25-triepoxy-3-{[beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranosyl]oxy}co-prostigmast-7-en-17-ol (2), (3R,16S,17R,20S,22R,24S,25S)-22,25-epoxy-3,27-bis(beta-D-glueopyranosyloxy)coprostigmast-7-en-16-ol (3), (3R,16S,17R,20S,22R,24S,25S)-22,25-epoxy-3-{[beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranosyl]oxy}-27-(beta-D-glucopyranosyloxy)coprostigmast-7-en-16-ol (4). and (3R,16R,17S,20R,22S,23S, 24S,25S)-22,25-epoxy-3-(beta-D-glucopyranosyloxy)coprostigmast-7-ene-16,17,23,27-tetrol 27-acetate (5) by means of 1D and 2D NMR spectroscopy and HR-MALDI mass spectrometry. The novel compounds, which consist of three additional ring systems at the coprostigmastane skeleton, were named ajugasalicioside A (1) and B (2), and the new compounds C (3), D (4) and E (5). In our cytotoxicity assays (HeLa cells, Jurkat T cells. and peripheral mononuclear blood cells), ajugasaliciosides A-D specifically inhibited the viability and growth of Jurkat T-leukemia cells at concentrations below 10 mum. Ajugasalicioside A (1; (IC50 = 6 mum) and C (3: IC50 = 3 mum) were the most active compounds. Ajugasalicioside A (1) induced cell-cell contact, inhibited Jurkat T cell proliferation, and up-regulated mRNA levels of the cell-cycle regulator cyclin D1, which might be an indication for cell differentiation. Furthermore, 1 down-regulated the mRNA levels of the NF-kappaB subunit p65 in a concentration-dependent manner. These effects were not found for ajugasalicioside B (2), which has an additional glucose unit, and the onset of cytotoxicity of 2 (IC50 = 10 mum) was delayed by 24 h.