Antileishmanial Activity of Parthenolide, a Sesquiterpene Lactone Isolated from Tanacetum parthenium

Abstract

The in vitro activity of parthenolide against Leishmania amazonensis was investigated. Parthenolide is a sesquiterpene lactone purified from the hydroalcoholic extract of aerial parts of Tanacetum parthenium. This isolated compound was identified through spectral analyses by UV, infrared, 1 H and 13 C nuclear magnetic resonance imaging, DEPT (distortionless enhancement by polarization transfer), COSY (correlated spectroscopy), HMQC (heteronuclear multiple-quantum coherence), and electron spray ionization-mass spectrometry. Parthenolide showed significant activity against the promastigote form of L. amazonensis, with 50% inhibition of cell growth at a concentration of 0.37 g/ml. For the intracellular amastigote form, parthenolide reduced by 50% the survival index of parasites in macrophages when it was used at 0.81 g/ml. The purified compound showed no cytotoxic effects against J774G8 macrophages in culture and did not cause lysis in sheep blood when it was used at higher concentrations that inhibited promastigote forms. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis with gelatin as the substrate showed that the enzymatic activity of the enzyme cysteine protease increased following treatment of the promastigotes with the isolated compound. This finding was correlated with marked morphological changes induced by parthenolide, such as the appearance of structures similar to large lysosomes and intense exocytic activity in the region of the flagellar pocket, as seen by electron microscopy. These results provide new perspectives on the development of novel drugs with leishmanicidal activities obtained from natural products.

Qualitative analysis of an ethanolic extract from Trametes versicolor and biological screening against Leishmania amazonensis.

“…The 50 % cytotoxic concentration (CC 50 ) was obtained from dose-response curves fi t to data by means of the equation for the sigmoidal E max model (Bodley et al, 1995). Selectivity indi ces (SI) were then calculated by dividing the CC 50 for peritoneal macrophages of BALB/c mice by the IC 50 for Leishmania promastigotes (Tiuman et al, 2005).…”

Leishmanicidal activity of Echinaster (Othilia) echinophorus crude extract

“…In parallel evaluation of the cytotoxicity of the extract against host cells, the extract showed a selectivity index (SI) of nine; this is particularly relevant since it has been reported that products with an SI value greater than one are considered to be more selective in their activity against parasites, while those with an SI value lower than one are considered more selective in their activity against host cells 6,32 . The SI shown by the extract of E. echinophorus indicated that the action of the extract is specific for the Leishmania parasites and that it is not toxic for mouse peritoneal macrophages.…”

Column Chromatography for Terpenoids and Flavonoids

“…Next, the CH 2 Cl 2 fraction was chromatographed on a silica gel column with different mixtures of solvents. The hexane-CH 2 Cl 2 fraction resulted in isolation of parthenolide (Robbers et al, 1998;Tiuman et al, 2005 …”