title: Activity of the julocrotine, a glutarimide alkaloid from Croton pullei var. glabrior, on Leishmania (L.) amazonensis.
abstract: The antiproliferative effect of julocrotine, an alkaloid isolated from Croton pullei var. glabrior (Euphorbiaceae), was studied in the macrophage amastigote and promastigote stages of the protozoan Leishmania (L.) amazonensis, which causes cutaneous leishmaniasis in the New World. Julocrotine showed a dose-dependent effect against the amastigote and promastigote forms, where 79 μM julocrotine inhibited promastigote growth by 54%, with an IC50 of 67 μM. To analyze the antiamastigote activity of the drug, murine peritoneal macrophages infected with L. amazonensis promastigotes were treated with different concentrations of julocrotine. An 80% inhibition of amastigote development was observed using 79 μM julocrotine for 72 h, with an IC50 of 19.8 μM. In addition, ultrastructural observation of the parasites showed a significant reduction in the number of amastigotes in the parasitophorous vacuoles and morphological changes in promastigotes, such as swelling of the mitochondrion, chromatin condensation, presence of membranous structures near the Golgi complex, and some vesicle bodies in the flagellar pocket. A colorimetric assay (MTT), which measures cytotoxic metabolic activity, showed that macrophages maintain their viability after treatment with the drug. These results suggest that julocrotine effectively inhibits the growth of parasites and does not have any cytototoxic effects on the host cell.
authors.affiliation: Laboratório de Parasitologia e Biologia Estrutural, Instituto de Ciências Biológicas, Universidade Federal do Pará, Av. Augusto Corrêa no.01, Bairro Guamá, 66075-110 Belém, Pará, Brazil.
authors.forename: Leda R C
authors.initials: LR
authors.lastname: Guimarães
authors.forename: Ana Paula D
authors.initials: AP
authors.lastname: Rodrigues
authors.forename: Patrícia S B
authors.initials: PS
authors.lastname: Marinho
authors.forename: Adolfo H
authors.initials: AH
authors.lastname: Muller
authors.forename: Giselle M S
authors.initials: GM
authors.lastname: Guilhon
authors.forename: Lourivaldo S
authors.initials: LS
authors.lastname: Santos
authors.forename: José Luiz M
authors.initials: JL
authors.lastname: do Nascimento
authors.forename: Edilene O
authors.initials: EO
authors.lastname: Silva
mesh_terms: D000470:Alkaloids / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D000981:Antiprotozoal Agents / Q000302:isolation & purification / Q000494:pharmacology*; D003124:Colorimetry / Q000379:methods; D029802:Croton / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D020128:Inhibitory Concentration 50; D007891:Leishmania / Q000187:drug effects* / Q000648:ultrastructure; D008264:Macrophages / Q000469:parasitology; D051379:Mice; D050296:Microbial Viability; D046529:Microscopy, Electron, Transmission; D015388:Organelles / Q000648:ultrastructure; D010274:Parasitology / Q000379:methods; D010881:Piperidones / Q000302:isolation & purification / Q000494:pharmacology*; D013778:Tetrazolium Salts / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism
chemical_list: D000470:Alkaloids; D000981:Antiprotozoal Agents; D010881:Piperidones; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue; C428864:julocrotine