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In vitro activities of two antimitotic compounds, pancratistatin and 7-deoxynarciclasine, against Encephalitozoon intestinalis, a microsporidium causing infections in humans.

Abstract
The antiparasitic effect of a collection of compounds with antimitotic activity has been tested on a mammalian cell line infected with Encephalitozoon intestinalis, a microsporidian causing intestinal and systemic infection in immunocompromised patients. The antiparasitic effect was evaluated by counting the number of parasitophorous vacuoles detected by immunofluorescence. Out of 526 compounds tested, 2 (pancratistatin and 7-deoxynarciclasine) inhibited the infection without affecting the host cell. The 50% inhibitory concentrations (IC(50)s) of pancratistatin and 7-deoxynarciclasine for E. intestinalis were 0.18 microM and 0.2 microM, respectively, approximately eightfold lower than the IC(50)s of these same compounds against the host cells. Electron microscopy confirmed the gradual decrease in the number of parasitophorous vacuoles and showed that of the two life cycle phases, sporogony was more sensitive to the inhibitors than merogony. Furthermore, the persistence of meronts in some cells apparently devoid of sporonts and spores indicated that the inhibitors block development rather than entry of the parasite into the host cell. The occurrence of binucleate sporoblasts and spores suggests that these inhibitors blocked a specific phase of cell division.
AuthorsM Ouarzane-Amara, J F Franetich, D Mazier, G R Pettit, L Meijer, C Doerig, I Desportes-Livage
JournalAntimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 45 Issue 12 Pg. 3409-15 (Dec 2001) ISSN: 0066-4804 [Print] United States
PMID11709316 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • 7-deoxynarciclasine
  • Amaryllidaceae Alkaloids
  • Antineoplastic Agents
  • Antineoplastic Agents, Phytogenic
  • Isoquinolines
  • pancratistatin
Topics
  • Amaryllidaceae Alkaloids
  • Animals
  • Antineoplastic Agents (pharmacology)
  • Antineoplastic Agents, Phytogenic (pharmacology)
  • Cell Division (drug effects)
  • Encephalitozoon (drug effects, growth & development, ultrastructure)
  • Encephalitozoonosis (parasitology)
  • Humans
  • Isoquinolines (pharmacology)
  • Microscopy, Electron
  • Spores (drug effects, ultrastructure)

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