Planta Med 2009; 75 - PD79
DOI: 10.1055/s-0029-1234558

Trypanocidal, leishmanicidal and cytotoxic effects of anthecotulide type linear sesquiterpene lactones from Anthemis auriculata

A Karioti 1, H Skaltsa 1, M Kaiser 2, D Tasdemir 3
  • 1Department of Pharmacognosy and Chemistry of Natural Products, School of Pharmacy, University of Athens, 15771 Athens, Greece
  • 2Department of Medical Parasitology, Swiss Tropical Institute, 4002 Basel, Switzerland
  • 3Centre for Pharmacognosy and Phytotherapy, School of Pharmacy, University of London, London WC1N 1AX, UK

Trypanosomiasis and leishmaniasis pose major public health threats for many tropical countries. We recently reported the antiprotozoal activiy of anthecularin (1), a minor sesquiterpene lactone (SL) with a novel ring system from Greek Anthemis auriculata [1]. In the current study, we evaluated the in vitro antiprotozoal and cytotoxic potential of anthecotulide (2), 4-hydroxyanthecotulide (3) and 4-acetoxyanthecotulide (4), irregular, linear SLs biosynthetically related to anthecularin, also obtained from the same plant [2]. Trypomastigote forms of Trypanosoma brucei rhodesiense and T. cruzi and axenic amastigotes of Leishmania donovani were used for testing. Cytotoxic potential of the compounds were also assessed against mammalian (rat) skeletal myoblasts (L6 cells). All compounds showed potent trypanocidal and leishmanicidal activity, which enabled us to draw some valuable SARs. Notably, 4-hydroxyanthecotulide (3) appeared to be the most active compound against all parasites, particularly towards T. b. rhodesiense (IC50 0.56µg/ml), whereas 4-acetoxyanthecotulide (4) was the least active. However, the compounds possessed toxicity (IC50 5.14–38.3µg/ml), which might limit their use as antiprotozoal agents.

References: [1] Karioti, A. et al. (2007)J. Org. Chem. 72:8103–8106.

[2] Theodori, R. et al. (2006)J. Nat. Prod. 69:662–664.