This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tiuman, T. S. Articles by Nakamura, C. V. Search for Related Content PubMed PubMed Citation Articles by Tiuman, T. S. Articles by Nakamura, C. V.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, January 2005, p. 176-182, Vol. 49, No. 1
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.11.176-182.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

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

Programa de Pós-graduação em Ciências Farmacêuticas,¹ Departamento de Farmácia e Farmacologia,³ Departamento de Análises Clínicas, Universidade Estadual de Maringá, Maringá, Paraná,² Grupo de Biologia Estrutural, Divisão de Biologia Celular, Centro de Pesquisa, Instituto Nacional de CÂncer,⁴ Laboratório de Ultraestrutura Celular Hertha Meyer, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Ilha do Fundão, Rio de Janeiro, Brazil⁵

Received 20 May 2004/ Returned for modification 24 June 2004/ Accepted 22 September 2004

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, ¹H and ¹³C 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 µg/ml. For the intracellular amastigote form, parthenolide reduced by 50% the survival index of parasites in macrophages when it was used at 0.81 µg/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.

This article has been cited by other articles:

• Sulsen, V. P., Frank, F. M., Cazorla, S. I., Anesini, C. A., Malchiodi, E. L., Freixa, B., Vila, R., Muschietti, L. V., Martino, V. S. (2008). Trypanocidal and Leishmanicidal Activities of Sesquiterpene Lactones from Ambrosia tenuifolia Sprengel (Asteraceae). Antimicrob. Agents Chemother. 52: 2415-2419 [Abstract] [Full Text]  
• Banerjee, A., Roychoudhury, J., Ali, N. (2008). Stearylamine-bearing cationic liposomes kill Leishmania parasites through surface exposed negatively charged phosphatidylserine. J Antimicrob Chemother 61: 103-110 [Abstract] [Full Text]