title: 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 microg/ml. For the intracellular amastigote form, parthenolide reduced by 50% the survival index of parasites in macrophages when it was used at 0.81 microg/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.
authors.affiliation: Departamento de Análises Clínicas, Universidade Estadual de Maringá, Bloco I-90 Sala 123 CCS, Av. Colombo 5790, BR-87020-900, Maringá, Paraná, Brazil.
authors.forename: Tatiana Shioji
authors.initials: TS
authors.lastname: Tiuman
authors.forename: Tânia
authors.initials: T
authors.lastname: Ueda-Nakamura
authors.forename: Diógenes Aparício
authors.initials: DA
authors.lastname: Garcia Cortez
authors.forename: Benedito Prado
authors.initials: BP
authors.lastname: Dias Filho
authors.forename: José Andrés
authors.initials: JA
authors.lastname: Morgado-Díaz
authors.forename: Wanderley
authors.initials: W
authors.lastname: de Souza
authors.forename: Celso Vataru
authors.initials: CV
authors.lastname: Nakamura
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D002460:Cell Line; D007783:Lactones / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D007891:Leishmania / Q000187:drug effects* / Q000254:growth & development; D008264:Macrophages; D051379:Mice; D021261:Parasitic Sensitivity Tests; D010936:Plant Extracts / Q000494:pharmacology; D012717:Sesquiterpenes / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D020903:Tanacetum parthenium / Q000737:chemistry*
chemical_list: D000981:Antiprotozoal Agents; D007783:Lactones; D010936:Plant Extracts; D012717:Sesquiterpenes; C002669:parthenolide