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Aryloxyethyl Thiocyanates Are Potent Growth Inhibitors of Trypanosoma cruzi and Toxoplasma gondii
Author(s) -
Chao María N.,
Matiuzzi Carolina Exeni,
Storey Melissa,
Li Catherine,
Szajnman Sergio H.,
Docampo Roberto,
Moreno Silvia N. J.,
Rodriguez Juan B.
Publication year - 2015
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201500100
Subject(s) - trypanosoma cruzi , toxoplasma gondii , antiparasitic , antiparasitic agent , toxoplasmosis , chagas disease , thiocyanate , biology , chemistry , mode of action , microbiology and biotechnology , stereochemistry , biochemistry , pharmacology , virology , immunology , parasite hosting , medicine , antibody , world wide web , computer science , pathology
As a part of our project aimed at searching for new safe chemotherapeutic agents against parasitic diseases, several compounds structurally related to the antiparasitic agent WC‐9 (4‐phenoxyphenoxyethyl thiocyanate), which were modified at the terminal phenyl ring, were designed, synthesized, and evaluated as growth inhibitors against Trypanosoma cruzi , the etiological agent of Chagas disease, and Toxoplasma gondii , the parasite responsible of toxoplasmosis. Most of the synthetic analogues exhibited similar antiparasitic activity and were slightly more potent than our lead WC‐9. For example, two trifluoromethylated derivatives exhibited ED 50 values of 10.0 and 9.2 μ M against intracellular T. cruzi , whereas they showed potent action against tachyzoites of T. gondii (ED 50 values of 1.6 and 1.9 μ M against T. gondii ). In addition, analogues of WC‐9 in which the terminal aryl group is in the meta position with respect to the alkyl chain bearing the thiocyanate group showed potent inhibitory action against both T. cruzi and T. gondii at the very low micromolar range, which suggests that a para ‐phenyl substitution pattern is not necessary for biological activity.