Planta Med 2010; 76 - P267
DOI: 10.1055/s-0030-1264565

Semisynthesis and pharmacological investigation of lipo-alkaloids prepared from aconitine by transesterification with eicosanoic acid analogues

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

Previously we reported the semisynthesis of 9 aconitine-derived lipo-alkaloids transesterified with fatty acids differing in the number of carbon atoms and double bonds in their chains [1]. When these compounds were tested for COX-1, COX-2 and LTB4 formation inhibitory activities it was found that 14-benzoylaconine-8-O-eicosapentaenoate exhibited notable activities through all three in vitro anti-inflammatory test systems (inhibition (%): COX-1: 54.51, COX-2: 66.07, LTB4: 45.96, at 50µM concentration). Although no data exist on the natural occurrence of aconitine derived lipo-alkaloids containing eicosanoic acid analogues at C-8, the prospective of further charting the possible structure-activity relationships of lipo-alkaloids is reinforced by papers dealing with the importance and natural roles of different unsaturated eicosanoic acid derivatives in the process of inflammation [2]. The present paper reports the semisynthesis of 7 eicosanoate analogues of aconitine-derived lipo-alkaloids, prepared according to the modified method of Bai et al [3]. In the reactions, aconitine was transesterified by eicosanoic, 11-eicosenoic, 8,11,14-eicosatrienoic, 11,14,17-eicosatrienoic, 8,11,14,17-eicosatetraenoic and 5,8,11,14,17-eicosapentaenoic 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. Purity of the obtained lipo-alkaloids was proved with the aid of NMR spectroscopy. The COX-1, COX-2 and LTB4 formation inhibitory activities of this eicosanoate lipo-alkaloid series were also investigated. It was observed that the 14-benzoylaconine-8-O-eicosapentaenoate has the highest activities (inhibition (%): COX-1: 82.84, COX-2: 33.67, at 50µM concentration) between the eicosanoate analogues.

References: 1. Borcsa, B. et al. (2009) Planta Med. 75: 910.

2. Rouzer, C. et al. (2009)J. Lipid Res. 50: S29–34.

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