Planta Med 2009; 75 - PA26
DOI: 10.1055/s-0029-1234351

Semisynthesis and pharmacological investigation of lipo-alkaloids prepared from aconitine

B Borcsa 1, U Widowitz 2, D Csupor 1, P Forgo 1, R Bauer 2, J Hohmann 1
  • 1Department of Pharmacognosy, University of Szeged, H-6720 Szeged, Eötvös u. 6., Hungary
  • 2Institute of Pharmaceutical Sciences, Department of Pharmacognosy, Karl-Franzens University Graz, Universitätsplatz 4, 8010 Graz, Austria

Processed aconite drugs are widely used in Eastern medicine, principally as painkillers and antirheumatic agents. Active constituents of these drugs are aconitine-type diterpene alkaloids, which exhibit a broad spectrum of pharmacological activities, including antinociceptive and anti-inflammatory effects [1,2]. Unfortunately, most of the aconitine-type alkaloids (aconitine, hypaconitine, mesaconitine) are highly toxic, in contrast to the lipo-alkaloids, which possess far more less toxicity due to the presence of long chain fatty acid moiety in the molecules at C-8. The traditional processing (usually boiling) of the crude aconite drugs afforded the increasing of the concentration of lipo-alkaloids. There is a presumption that these compounds possess anti-inflammatory activity depending on the type of the ester group. Therefore, the aim of our work was to prepare a series of lipo-alkaloids, investigate their anti-inflammatory activity, and establish the correlation between the effect and the quality of the esterifying fatty acids.

The present paper reports the semisynthesis of aconitine-derived lipo-alkaloids, prepared according to the modified method of Bai et al [3]. In the reactions, aconitine was esterified by palmitic, stearic, lauric, myristic, palmitoleic, oleic, α- and γ-linolenic, linoleic, eicosapentaenoic and docosahexaenoic acids resulting the corresponding 14-benzoylaconin-8-O-esters and pyroaconitine. The reaction mixtures were purified of necessity by gelfiltration, preparative TLC and centrifugal planar chromatography. The structures were proved with the aid of 1H-NMR, JMOD spectra, further, 1H and 13C NMR assignments were determined for all compounds on the basis of 1H,1H-COSY, NOESY, HSQC and HMBC experiments. The COX-1, COX-2 and LTB4 formation inhibitory activity of the lipo-alkaloids were investigated, and found that especially compounds having unsaturated ester groups demonstrated remarkable COX-2 inhibitory activities.

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[2] González-Coloma, A. et al. (2004)J. Chem. Ecol. 30:1393–1408.

[3] Bai, Y. et al. (1994)J. Nat. Prod. 57:963–970.