Wednesday, April 29, 2015

Aryloxyethyl Thiocyanates Are Potent Growth Inhibitors of Trypanosoma cruzi and Toxoplasma gondii

2015 Apr 27. doi: 10.1002/cmdc.201500100. [Epub ahead of print]
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 ED50 values of 10.0 and 9.2 μM against intracellular T. cruzi, whereas they showed potent action against tachyzoites of T. gondii (ED50 values of 1.6 and 1.9 μM 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.
© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


antiparasitic agents; biological activity; chemotherapeutic agents; inhibitors; structure-activity relationships
[PubMed - as supplied by publisher]

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