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

ChemMedChem. 2015 Apr 27. doi: 10.1002/cmdc.201500100. [Epub ahead of print]

 

Chao MN¹, Matiuzzi CE, Storey M, Li C, Szajnman SH, Docampo R, Moreno SN, Rodriguez JB.

 

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.

KEYWORDS:

antiparasitic agents; biological activity; chemotherapeutic agents; inhibitors; structure-activity relationships

PMID:

25914175

[PubMed - as supplied by publisher]