Trypanosoma cruzi is the ethiological agent of Chagas
disease. New compounds are being developed based on the biosynthesis and
function of sterols, because T. cruzi has a requirement for
specific endogenous sterols for growth and survival. Sterol biosynthesis
inhibitors (SBIs) are drugs commonly used against fungal diseases. These
drugs act by depleting essential and specific membrane components
and/or inducing the accumulation of toxic intermediary or lateral
products of the biosynthetic pathway. In this work we present the effects
of WSP488, WSP501, and WSP561, specific inhibitors of
Δ24(25)-sterol methyl transferase, on the ultrastructure of
T. cruzi epimastigotes. All three drugs inhibited parasite
multiplication at low concentrations, with IC50 values of 0.48,
0.44, and 0.48 μM, respectively, and induced marked morphological
changes including (a) blockage of cell division; (b) swelling of the
mitochondrion, with several projections and depressions; (c) swelling of
the perinuclear space; (d) presence of autophagosomes and myelin-like
figures; (e) enlargement of the flagellar pocket and of a cytoplasmic
vacuole located in close association with the flagellar pocket; (f)
detachment of the membrane of the cell body; and (g) formation of a
vesicle at the surface of the parasite between the flagellar pocket and
the cytostome. Our results show that these drugs are potent in
vitro inhibitors of growth of T. cruzi.