Activity of the julocrotine, a glutarimide alkaloid from Croton pullei var. glabrior, on Leishmania (L.) amazonensis

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 sho...

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Published in:	Parasitology research (1987) Vol. 107; no. 5; pp. 1075 - 1081
Main Authors:	Guimarães, Leda R. C., Rodrigues, Ana Paula D., Marinho, Patrícia S. B., Muller, Adolfo H., Guilhon, Giselle M. S., Santos, Lourivaldo S., do Nascimento, José Luiz M., Silva, Edilene O.
Format:	Journal Article
Language:	English
Published:	Berlin/Heidelberg Springer-Verlag 01-10-2010 Springer
Subjects:	Alkaloids Alkaloids - isolation & purification Alkaloids - pharmacology Amastigotes Analysis Animals Antibiotics. Antiinfectious agents. Antiparasitic agents Antiparasitic agents Antiprotozoal Agents - isolation & purification Antiprotozoal Agents - pharmacology Biological and medical sciences Biomedical and Life Sciences Biomedicine Chromatin Colorimetry Colorimetry - methods Condensation Croton Croton - chemistry Cutaneous leishmaniasis Cytotoxicity Dose-Response Relationship, Drug Drugs Euphorbiaceae Flagella Golgi apparatus Immunology Inhibitory Concentration 50 Leishmania Leishmania - drug effects Leishmania - ultrastructure Macrophages Macrophages - parasitology Medical Microbiology Medical sciences Mice Microbial Viability Microbiology Microscopy, Electron, Transmission Organelles - ultrastructure Original Paper Parasitology - methods parasitophorous vacuole Peritoneum Pharmacology. Drug treatments Piperidones - isolation & purification Piperidones - pharmacology Promastigotes Tetrazolium Salts - metabolism Thiazoles - metabolism Vesicles Cutaneous Leishmaniasis Miltefosine Leishmaniasis Croton Visceral Leishmaniasis Kinetoplastida Protozoa Toxicity Parasite Activity Alkaloid Dicotyledones Pathogenic Angiospermae Plant origin Parasiticide Euphorbiaceae Spermatophyta Leishmania amazonensis
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Summary:	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.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23
ISSN:	0932-0113 1432-1955
DOI:	10.1007/s00436-010-1973-0