Search

Abstract: Trypanosomiasis and leishmaniasis pose major public health threats for many countries, particularly those in sub-Saharan Africa and South America. In the present study, we evaluated the in vitro antiprotozoal activity of three irregular, linear sesquiterpene lactones recently isolated from Greek Anthemis auriculata, namely anthecotulide (1), 4-hydroxyanthecotulide (2) and 4-acetoxyanthecotulide (3). Trypomastigote forms of Trypanosoma brucei rhodesiense and T. cruzi as well as axenic amastigotes of Leishmania donovani were used for testing. The cytotoxic potential of the compounds was also assessed against mammalian (rat) skeletal myoblasts (L6 cells). All compounds showed potent trypanocidal and leishmanicidal activity. 4-Hydroxyanthecotulide (2) appeared to be the most active compound against all parasites, particularly towards T. b. rhodesiense (IC50 0.56μg/ml), whereas 4-acetoxyanthecotulide (3) was the least active. All three metabolites possessed toxicity on mammalian cells, which might limit their use as antiprotozoal agents. [Copyright &y& Elsevier]

Abstract: Enoyl-ACP reductase (FabI) is a key enzyme of the type II fatty acid biosynthesis (FAS-II) pathway and a validated antimicrobial target. In the current study, three linear sesquiterpene lactones obtained from Anthemis auriculata, namely anthecotulide (1), 4-hydroxyanthecotulide (2) and 4-acetoxyanthecotulide (3) were evaluated for specific inhibitory effects against the FabI enzyme from three pathogenic microorganisms, Plasmodium falciparum (PfFabI), Mycobacterium tuberculosis (MtFabI) and Escherichia coli (EcFabI). In addition, the compounds were also tested against two elongation enzymes from the plasmodial FAS-II system, β-ketoacyl-ACP reductase (PfFabG) and β-hydroxyacyl-ACP deydratase (PfFabZ). The compounds showed clear differentiation in inhibition of FabI enzymes from different microorganisms. Anthecotulide (1) was most active against MtFabI (IC50 4.5μg/ml), whereas the oxygenated derivatives thereof (compounds 2 and 3) specifically inhibited plasmodial FAS-II enzymes, PfFabI and PfFabG (IC50 values 20–75μg/ml). All compounds were inactive towards EcFabI. In whole cell assays, all three compounds exhibited antimalarial and antibacterial activities. [Copyright &y& Elsevier]