Aryloxyethyl thiocyanates are potent growth inhibitors of Trypanosoma cruzi and Toxoplasma gondii
Abstract 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, synthesize...
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| Acceso en línea: | http://hdl.handle.net/20.500.12110/paper_18607179_v10_n6_p1094_Chao |
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todo:paper_18607179_v10_n6_p1094_Chao2023-10-03T16:33:19Z Aryloxyethyl thiocyanates are potent growth inhibitors of Trypanosoma cruzi and Toxoplasma gondii Chao, M.N. Matiuzzi, C.E. Storey, M. Li, C. Szajnman, S.H. Docampo, R. Moreno, S.N.J. Rodriguez, J.B. antiparasitic agents biological activity chemotherapeutic agents inhibitors structure-activity relationships 3 (2 chlorophenoxy)phenoxyethanol 3 (2 chlorophenoxy)phenoxyethyl 4 toluenesulfonate 3 (2 chlorophenoxy)phenoxyethyl tetrahydro 2h pyran 2 yl ether 3 (2 chlorophenoxy)phenoxyethyl thiocyanate 3 (3 chlorophenoxy)phenoxyethyl tetrahydro 2h pyran 2 yl ether 4 (pyridin 2 yloxy)phenoxyethanol 4 (pyridin 2 yloxy)phenoxyethyl 4 toluenesulfonate 4 (pyridin 2 yloxy)phenoxyethyl tetrahydro 2h pyran 2 yl ether 4 (pyridin 2 yloxy)phenoxyethyl thiocyanate 4 benzyloxyphenoxyethyl tetrahydro 2h pyran 2 yl ether 4 hydroxyphenoxyethyl tetrahydro 2h pyran 2 yl ether 4 [(3 trifluoro)phenoxy]phenoxyethanol 4 [(3 trifluoro)phenoxy]phenoxyethyl 4 toluenesulfonate 4 [(3 trifluoro)phenoxy]phenoxyethyl tetrahydro 2h pyran 2 yl ether 4 [(3 trifluoro)phenoxy]phenoxyethyl thiocyanate 4 [(4 trifluoro)phenoxy]phenoxyethanol 4 [(4 trifluoro)phenoxy]phenoxyethyl 4 toluenesulfonate 4 [(4 trifluoro)phenoxy]phenoxyethyl tetrahydro 2h pyran 2 yl ether 4 [(4 trifluoro)phenoxy]phenoxyethyl thiocyanate alpha naphthyloxyphenylethanol alpha naphthyloxyphenylethyl 4 toluenesulfonate alpha naphthyloxyphenylethyl tetrahydro 2h pyran 2 yl ether alpha naphthyloxyphenylethyl thiocyanate antiparasitic agent aryloxyethyl thiocyanate derivative beta naphthyloxyphenoxyethanol beta naphthyloxyphenoxyethyl 4 toluenesulfonate beta naphthyloxyphenoxyethyl tetrahydro 2h pyran 2 yl ether thiocyanic acid derivative unclassified drug unindexed drug antiprotozoal agent thiocyanate thiocyanic acid derivative antiparasitic activity antiprotozoal activity Article Chagas disease crystal structure cytotoxicity drug screening drug structure drug synthesis in vitro study microbial growth nuclear magnetic resonance priority journal tachyzoite Toxoplasma gondii toxoplasmosis Trypanosoma cruzi Vero cell line animal Chlorocebus aethiops drug effects growth, development and aging Toxoplasma Trypanosoma cruzi Animals Antiprotozoal Agents Cercopithecus aethiops Thiocyanates Toxoplasma Trypanosoma cruzi Vero Cells Abstract 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. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_18607179_v10_n6_p1094_Chao |
| institution |
Universidad de Buenos Aires |
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I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
antiparasitic agents biological activity chemotherapeutic agents inhibitors structure-activity relationships 3 (2 chlorophenoxy)phenoxyethanol 3 (2 chlorophenoxy)phenoxyethyl 4 toluenesulfonate 3 (2 chlorophenoxy)phenoxyethyl tetrahydro 2h pyran 2 yl ether 3 (2 chlorophenoxy)phenoxyethyl thiocyanate 3 (3 chlorophenoxy)phenoxyethyl tetrahydro 2h pyran 2 yl ether 4 (pyridin 2 yloxy)phenoxyethanol 4 (pyridin 2 yloxy)phenoxyethyl 4 toluenesulfonate 4 (pyridin 2 yloxy)phenoxyethyl tetrahydro 2h pyran 2 yl ether 4 (pyridin 2 yloxy)phenoxyethyl thiocyanate 4 benzyloxyphenoxyethyl tetrahydro 2h pyran 2 yl ether 4 hydroxyphenoxyethyl tetrahydro 2h pyran 2 yl ether 4 [(3 trifluoro)phenoxy]phenoxyethanol 4 [(3 trifluoro)phenoxy]phenoxyethyl 4 toluenesulfonate 4 [(3 trifluoro)phenoxy]phenoxyethyl tetrahydro 2h pyran 2 yl ether 4 [(3 trifluoro)phenoxy]phenoxyethyl thiocyanate 4 [(4 trifluoro)phenoxy]phenoxyethanol 4 [(4 trifluoro)phenoxy]phenoxyethyl 4 toluenesulfonate 4 [(4 trifluoro)phenoxy]phenoxyethyl tetrahydro 2h pyran 2 yl ether 4 [(4 trifluoro)phenoxy]phenoxyethyl thiocyanate alpha naphthyloxyphenylethanol alpha naphthyloxyphenylethyl 4 toluenesulfonate alpha naphthyloxyphenylethyl tetrahydro 2h pyran 2 yl ether alpha naphthyloxyphenylethyl thiocyanate antiparasitic agent aryloxyethyl thiocyanate derivative beta naphthyloxyphenoxyethanol beta naphthyloxyphenoxyethyl 4 toluenesulfonate beta naphthyloxyphenoxyethyl tetrahydro 2h pyran 2 yl ether thiocyanic acid derivative unclassified drug unindexed drug antiprotozoal agent thiocyanate thiocyanic acid derivative antiparasitic activity antiprotozoal activity Article Chagas disease crystal structure cytotoxicity drug screening drug structure drug synthesis in vitro study microbial growth nuclear magnetic resonance priority journal tachyzoite Toxoplasma gondii toxoplasmosis Trypanosoma cruzi Vero cell line animal Chlorocebus aethiops drug effects growth, development and aging Toxoplasma Trypanosoma cruzi Animals Antiprotozoal Agents Cercopithecus aethiops Thiocyanates Toxoplasma Trypanosoma cruzi Vero Cells |
| spellingShingle |
antiparasitic agents biological activity chemotherapeutic agents inhibitors structure-activity relationships 3 (2 chlorophenoxy)phenoxyethanol 3 (2 chlorophenoxy)phenoxyethyl 4 toluenesulfonate 3 (2 chlorophenoxy)phenoxyethyl tetrahydro 2h pyran 2 yl ether 3 (2 chlorophenoxy)phenoxyethyl thiocyanate 3 (3 chlorophenoxy)phenoxyethyl tetrahydro 2h pyran 2 yl ether 4 (pyridin 2 yloxy)phenoxyethanol 4 (pyridin 2 yloxy)phenoxyethyl 4 toluenesulfonate 4 (pyridin 2 yloxy)phenoxyethyl tetrahydro 2h pyran 2 yl ether 4 (pyridin 2 yloxy)phenoxyethyl thiocyanate 4 benzyloxyphenoxyethyl tetrahydro 2h pyran 2 yl ether 4 hydroxyphenoxyethyl tetrahydro 2h pyran 2 yl ether 4 [(3 trifluoro)phenoxy]phenoxyethanol 4 [(3 trifluoro)phenoxy]phenoxyethyl 4 toluenesulfonate 4 [(3 trifluoro)phenoxy]phenoxyethyl tetrahydro 2h pyran 2 yl ether 4 [(3 trifluoro)phenoxy]phenoxyethyl thiocyanate 4 [(4 trifluoro)phenoxy]phenoxyethanol 4 [(4 trifluoro)phenoxy]phenoxyethyl 4 toluenesulfonate 4 [(4 trifluoro)phenoxy]phenoxyethyl tetrahydro 2h pyran 2 yl ether 4 [(4 trifluoro)phenoxy]phenoxyethyl thiocyanate alpha naphthyloxyphenylethanol alpha naphthyloxyphenylethyl 4 toluenesulfonate alpha naphthyloxyphenylethyl tetrahydro 2h pyran 2 yl ether alpha naphthyloxyphenylethyl thiocyanate antiparasitic agent aryloxyethyl thiocyanate derivative beta naphthyloxyphenoxyethanol beta naphthyloxyphenoxyethyl 4 toluenesulfonate beta naphthyloxyphenoxyethyl tetrahydro 2h pyran 2 yl ether thiocyanic acid derivative unclassified drug unindexed drug antiprotozoal agent thiocyanate thiocyanic acid derivative antiparasitic activity antiprotozoal activity Article Chagas disease crystal structure cytotoxicity drug screening drug structure drug synthesis in vitro study microbial growth nuclear magnetic resonance priority journal tachyzoite Toxoplasma gondii toxoplasmosis Trypanosoma cruzi Vero cell line animal Chlorocebus aethiops drug effects growth, development and aging Toxoplasma Trypanosoma cruzi Animals Antiprotozoal Agents Cercopithecus aethiops Thiocyanates Toxoplasma Trypanosoma cruzi Vero Cells Chao, M.N. Matiuzzi, C.E. Storey, M. Li, C. Szajnman, S.H. Docampo, R. Moreno, S.N.J. Rodriguez, J.B. Aryloxyethyl thiocyanates are potent growth inhibitors of Trypanosoma cruzi and Toxoplasma gondii |
| topic_facet |
antiparasitic agents biological activity chemotherapeutic agents inhibitors structure-activity relationships 3 (2 chlorophenoxy)phenoxyethanol 3 (2 chlorophenoxy)phenoxyethyl 4 toluenesulfonate 3 (2 chlorophenoxy)phenoxyethyl tetrahydro 2h pyran 2 yl ether 3 (2 chlorophenoxy)phenoxyethyl thiocyanate 3 (3 chlorophenoxy)phenoxyethyl tetrahydro 2h pyran 2 yl ether 4 (pyridin 2 yloxy)phenoxyethanol 4 (pyridin 2 yloxy)phenoxyethyl 4 toluenesulfonate 4 (pyridin 2 yloxy)phenoxyethyl tetrahydro 2h pyran 2 yl ether 4 (pyridin 2 yloxy)phenoxyethyl thiocyanate 4 benzyloxyphenoxyethyl tetrahydro 2h pyran 2 yl ether 4 hydroxyphenoxyethyl tetrahydro 2h pyran 2 yl ether 4 [(3 trifluoro)phenoxy]phenoxyethanol 4 [(3 trifluoro)phenoxy]phenoxyethyl 4 toluenesulfonate 4 [(3 trifluoro)phenoxy]phenoxyethyl tetrahydro 2h pyran 2 yl ether 4 [(3 trifluoro)phenoxy]phenoxyethyl thiocyanate 4 [(4 trifluoro)phenoxy]phenoxyethanol 4 [(4 trifluoro)phenoxy]phenoxyethyl 4 toluenesulfonate 4 [(4 trifluoro)phenoxy]phenoxyethyl tetrahydro 2h pyran 2 yl ether 4 [(4 trifluoro)phenoxy]phenoxyethyl thiocyanate alpha naphthyloxyphenylethanol alpha naphthyloxyphenylethyl 4 toluenesulfonate alpha naphthyloxyphenylethyl tetrahydro 2h pyran 2 yl ether alpha naphthyloxyphenylethyl thiocyanate antiparasitic agent aryloxyethyl thiocyanate derivative beta naphthyloxyphenoxyethanol beta naphthyloxyphenoxyethyl 4 toluenesulfonate beta naphthyloxyphenoxyethyl tetrahydro 2h pyran 2 yl ether thiocyanic acid derivative unclassified drug unindexed drug antiprotozoal agent thiocyanate thiocyanic acid derivative antiparasitic activity antiprotozoal activity Article Chagas disease crystal structure cytotoxicity drug screening drug structure drug synthesis in vitro study microbial growth nuclear magnetic resonance priority journal tachyzoite Toxoplasma gondii toxoplasmosis Trypanosoma cruzi Vero cell line animal Chlorocebus aethiops drug effects growth, development and aging Toxoplasma Trypanosoma cruzi Animals Antiprotozoal Agents Cercopithecus aethiops Thiocyanates Toxoplasma Trypanosoma cruzi Vero Cells |
| description |
Abstract 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. |
| format |
JOUR |
| author |
Chao, M.N. Matiuzzi, C.E. Storey, M. Li, C. Szajnman, S.H. Docampo, R. Moreno, S.N.J. Rodriguez, J.B. |
| author_facet |
Chao, M.N. Matiuzzi, C.E. Storey, M. Li, C. Szajnman, S.H. Docampo, R. Moreno, S.N.J. Rodriguez, J.B. |
| author_sort |
Chao, M.N. |
| title |
Aryloxyethyl thiocyanates are potent growth inhibitors of Trypanosoma cruzi and Toxoplasma gondii |
| title_short |
Aryloxyethyl thiocyanates are potent growth inhibitors of Trypanosoma cruzi and Toxoplasma gondii |
| title_full |
Aryloxyethyl thiocyanates are potent growth inhibitors of Trypanosoma cruzi and Toxoplasma gondii |
| title_fullStr |
Aryloxyethyl thiocyanates are potent growth inhibitors of Trypanosoma cruzi and Toxoplasma gondii |
| title_full_unstemmed |
Aryloxyethyl thiocyanates are potent growth inhibitors of Trypanosoma cruzi and Toxoplasma gondii |
| title_sort |
aryloxyethyl thiocyanates are potent growth inhibitors of trypanosoma cruzi and toxoplasma gondii |
| url |
http://hdl.handle.net/20.500.12110/paper_18607179_v10_n6_p1094_Chao |
| work_keys_str_mv |
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| _version_ |
1807320017394466816 |