Trypanosomatids possess an unremitting requirement for distinctive
endogenous sterols for their life cycle and cannot use the copious availability of
cholesterol existing in their mammalian hosts. Exhaustion of endogenous sterols
such as ergosterol or of its next biosynthetic product 24-ethylcholesta-5,7,22-trien-
3β-ol brings forth an inhibition of proliferation on Trypanosoma cruzi, the etiologic
agent of American trypanosomiasis or Chagas disease. These metabolites are
crucial; consequently, the enzymes implicated in catalyzing their formation
constitute interesting molecular targets for drug design. Selective inhibition of an
enzyme associated to the ergosterol biosynthesis will produce T. cruzi cell arrest.
Trypanosomatids, fungi, and yeasts have need of these endogenous sterols for cell
viability and growth. In fact, some effective ergosterol biosynthesis inhibitors bearing suitable
pharmacokinetic properties in mammals have become putative antiparasitic agents by inducing almost
complete parasitological cure in both acute and chronic experimental Chagas disease. WC-9 (compound
7; 4-phenoxyphenoxyethyl thiocyanate) holds our attention bearing in mind that this compound exhibits
ED50 values at the low nanomolar range against the clinically more relevant replicative form of T. cruzi
(amastigotes). The cellular activity of WC-9 is due to an exhaustion of endogenous sterols
demonstrating a blockade of the biosynthetic pathway at a pre-squalene level.
Keywords: Antiparasitic Agents, Chagas disease, Squalene synthase, Toxoplasmosis, WC-9.
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