title: Evaluation of three novel azasterols against Toxoplasma gondii.
abstract: Previous studies from our group have demonstrated the high susceptibility of Toxoplasma gondii tachyzoites to the sterol analogues 22,26-azasterol and 24,25-(R,S)-epiminolanosterol. In this work we present data on testing in vitro three novel azasterols as potential agents for the treatment of toxoplasmosis. The three compounds inhibited parasite growth at micromolar concentrations, in a dose-dependent manner. Electron microscopy analysis of intracellular tachyzoites after treatment with the most effective compound showed drastic mitochondrion swelling associated with the appearance of an electron-lucent matrix and disrupted cristae. Parasite lysis also took place. The appearance of electron dense cytoplasmic structures similar to amylopectin granules distributed throughout the parasite suggests that azasterols might be inducing differentiation of those tachyzoites which were not lysed to the bradyzoite stage.
authors.affiliation: Laboratório de Ultraestrutura Celular Herth, Meyer, Instituto de Biofísica Carlos Chagas Filho, UFRJ, CCS, Bloco G, Av. Carlo, Chagas Filho, Cidade Universitária, Ilha do Fundão, 21941-902, Rio de Janeiro, RJ, Brazil.
authors.forename: Erica S
authors.initials: ES
authors.lastname: Martins-Duarte
authors.forename: Leandro
authors.initials: L
authors.lastname: Lemgruber
authors.forename: Silvia Orenes
authors.initials: SO
authors.lastname: Lorente
authors.forename: Ludovic
authors.initials: L
authors.lastname: Gros
authors.forename: Filippo
authors.initials: F
authors.lastname: Magaraci
authors.forename: Ian H
authors.initials: IH
authors.lastname: Gilbert
authors.forename: Wanderley
authors.initials: W
authors.lastname: de Souza
authors.forename: Rossiane C
authors.initials: RC
authors.lastname: Vommaro
mesh_terms: D000818:Animals; D003049:Coccidiostats / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D013261:Sterols / Q000737:chemistry / Q000494:pharmacology*; D014122:Toxoplasma / Q000187:drug effects*
chemical_list: D003049:Coccidiostats; D013261:Sterols