Design, synthesis and biological evaluation of WC-9 analogs as antiparasitic agents

As a part of our project pointed at the search of new safe chemotherapeutic and chemoprophylactic agents against parasitic diseases, several compounds structurally related to 4-phenoxyphenoxyethyl thiocyanate (WC-9), which were modified at the terminal aromatic ring, were designed, synthesized and e...

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Autores principales:	Szajnman, Sergio Hernán, Moreno, Silvia N. J., Rodríguez, Juan Bautista
Publicado:	2013
Materias:	Antiparasitic agents Chagas disease Squalene synthase inhibitors Toxoplasma gondii WC-9 analogs Toxoplasmosis Trypanosoma cruzi 3 (4 methoxyphenoxy)phenoxyethyl thiocyanate 3 phenoxyphenoxyethyl thiocyanate 4 (3 methoxyphenoxy)phenoxyethyl thiocyanate 4 (3 nitrophenoxy)phenoxyethyl tetrahydro 2h pyran 2 yl ether 4 (3 nitrophenoxy)phenoxyethyl thiocyanate 4 (4 methoxyphenoxy)phenoxyethyl thiocyanate 4 (pyridin 3 yloxy)phenoxyethyl tetrahydro 2h pyran 2 yl ether 4 (pyridin 3 yloxy)phenoxyethyl thiocyanate 4 phenoxyphenoxyethyl thiocyanate antiparasitic agent atovaquone benznidazole nitro derivative thiocyanic acid derivative unclassified drug antiproliferative activity article biological activity controlled study drug cytotoxicity drug design drug screening drug synthesis nonhuman tachyzoite Toxoplasma gondii toxoplasmosis WC-9 analogs Antiparasitic Agents Dose-Response Relationship, Drug Drug Design Molecular Structure Parasitic Sensitivity Tests Phenyl Ethers Structure-Activity Relationship Thiocyanates Toxoplasma
Acceso en línea:	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_02235234_v69_n_p480_Elicio http://hdl.handle.net/20.500.12110/paper_02235234_v69_n_p480_Elicio
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

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spelling	paper:paper_02235234_v69_n_p480_Elicio2025-07-30T18:00:07Z Design, synthesis and biological evaluation of WC-9 analogs as antiparasitic agents Szajnman, Sergio Hernán Moreno, Silvia N. J. Rodríguez, Juan Bautista Antiparasitic agents Chagas disease Squalene synthase inhibitors Toxoplasma gondii WC-9 analogs Toxoplasmosis Trypanosoma cruzi 3 (4 methoxyphenoxy)phenoxyethyl thiocyanate 3 phenoxyphenoxyethyl thiocyanate 4 (3 methoxyphenoxy)phenoxyethyl thiocyanate 4 (3 nitrophenoxy)phenoxyethyl tetrahydro 2h pyran 2 yl ether 4 (3 nitrophenoxy)phenoxyethyl thiocyanate 4 (4 methoxyphenoxy)phenoxyethyl thiocyanate 4 (pyridin 3 yloxy)phenoxyethyl tetrahydro 2h pyran 2 yl ether 4 (pyridin 3 yloxy)phenoxyethyl thiocyanate 4 phenoxyphenoxyethyl thiocyanate antiparasitic agent atovaquone benznidazole nitro derivative thiocyanic acid derivative unclassified drug antiproliferative activity article biological activity Chagas disease controlled study drug cytotoxicity drug design drug screening drug synthesis nonhuman tachyzoite Toxoplasma gondii toxoplasmosis Trypanosoma cruzi Antiparasitic agents Chagas disease Squalene synthase inhibitors Toxoplasma gondii Toxoplasmosis Trypanosoma cruzi WC-9 analogs Antiparasitic Agents Dose-Response Relationship, Drug Drug Design Molecular Structure Parasitic Sensitivity Tests Phenyl Ethers Structure-Activity Relationship Thiocyanates Toxoplasma Trypanosoma cruzi As a part of our project pointed at the search of new safe chemotherapeutic and chemoprophylactic agents against parasitic diseases, several compounds structurally related to 4-phenoxyphenoxyethyl thiocyanate (WC-9), which were modified at the terminal aromatic ring, were designed, synthesized and evaluated as antiproliferative agents against Trypanosoma cruzi, the parasite responsible of American trypanosomiasis (Chagas disease) and Toxoplasma gondii, the etiological agent of toxoplasmosis. Most of the synthetic analogs exhibited similar antiparasitic activity being slightly more potent than the reference compound WC-9. For example, the nitro derivative 13 showed an ED50 value of 5.2 μM. Interestingly, the regioisomer of WC-9, compound 36 showed similar inhibitory action than WC-9 indicating that para-phenyl substitution pattern is not necessarily required for biological activity. The biological evaluation against T. gondii was also very promising. The ED50 values corresponding for 13, 36 and 37 were at the very low micromolar level against tachyzoites of T. gondii. © 2013 Elsevier Masson SAS. All rights reserved. Fil:Szajnman, S.H. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Moreno, S.N.J. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Rodriguez, J.B. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2013 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_02235234_v69_n_p480_Elicio http://hdl.handle.net/20.500.12110/paper_02235234_v69_n_p480_Elicio
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	Antiparasitic agents Chagas disease Squalene synthase inhibitors Toxoplasma gondii WC-9 analogs Toxoplasmosis Trypanosoma cruzi 3 (4 methoxyphenoxy)phenoxyethyl thiocyanate 3 phenoxyphenoxyethyl thiocyanate 4 (3 methoxyphenoxy)phenoxyethyl thiocyanate 4 (3 nitrophenoxy)phenoxyethyl tetrahydro 2h pyran 2 yl ether 4 (3 nitrophenoxy)phenoxyethyl thiocyanate 4 (4 methoxyphenoxy)phenoxyethyl thiocyanate 4 (pyridin 3 yloxy)phenoxyethyl tetrahydro 2h pyran 2 yl ether 4 (pyridin 3 yloxy)phenoxyethyl thiocyanate 4 phenoxyphenoxyethyl thiocyanate antiparasitic agent atovaquone benznidazole nitro derivative thiocyanic acid derivative unclassified drug antiproliferative activity article biological activity Chagas disease controlled study drug cytotoxicity drug design drug screening drug synthesis nonhuman tachyzoite Toxoplasma gondii toxoplasmosis Trypanosoma cruzi Antiparasitic agents Chagas disease Squalene synthase inhibitors Toxoplasma gondii Toxoplasmosis Trypanosoma cruzi WC-9 analogs Antiparasitic Agents Dose-Response Relationship, Drug Drug Design Molecular Structure Parasitic Sensitivity Tests Phenyl Ethers Structure-Activity Relationship Thiocyanates Toxoplasma Trypanosoma cruzi
spellingShingle	Antiparasitic agents Chagas disease Squalene synthase inhibitors Toxoplasma gondii WC-9 analogs Toxoplasmosis Trypanosoma cruzi 3 (4 methoxyphenoxy)phenoxyethyl thiocyanate 3 phenoxyphenoxyethyl thiocyanate 4 (3 methoxyphenoxy)phenoxyethyl thiocyanate 4 (3 nitrophenoxy)phenoxyethyl tetrahydro 2h pyran 2 yl ether 4 (3 nitrophenoxy)phenoxyethyl thiocyanate 4 (4 methoxyphenoxy)phenoxyethyl thiocyanate 4 (pyridin 3 yloxy)phenoxyethyl tetrahydro 2h pyran 2 yl ether 4 (pyridin 3 yloxy)phenoxyethyl thiocyanate 4 phenoxyphenoxyethyl thiocyanate antiparasitic agent atovaquone benznidazole nitro derivative thiocyanic acid derivative unclassified drug antiproliferative activity article biological activity Chagas disease controlled study drug cytotoxicity drug design drug screening drug synthesis nonhuman tachyzoite Toxoplasma gondii toxoplasmosis Trypanosoma cruzi Antiparasitic agents Chagas disease Squalene synthase inhibitors Toxoplasma gondii Toxoplasmosis Trypanosoma cruzi WC-9 analogs Antiparasitic Agents Dose-Response Relationship, Drug Drug Design Molecular Structure Parasitic Sensitivity Tests Phenyl Ethers Structure-Activity Relationship Thiocyanates Toxoplasma Trypanosoma cruzi Szajnman, Sergio Hernán Moreno, Silvia N. J. Rodríguez, Juan Bautista Design, synthesis and biological evaluation of WC-9 analogs as antiparasitic agents
topic_facet	Antiparasitic agents Chagas disease Squalene synthase inhibitors Toxoplasma gondii WC-9 analogs Toxoplasmosis Trypanosoma cruzi 3 (4 methoxyphenoxy)phenoxyethyl thiocyanate 3 phenoxyphenoxyethyl thiocyanate 4 (3 methoxyphenoxy)phenoxyethyl thiocyanate 4 (3 nitrophenoxy)phenoxyethyl tetrahydro 2h pyran 2 yl ether 4 (3 nitrophenoxy)phenoxyethyl thiocyanate 4 (4 methoxyphenoxy)phenoxyethyl thiocyanate 4 (pyridin 3 yloxy)phenoxyethyl tetrahydro 2h pyran 2 yl ether 4 (pyridin 3 yloxy)phenoxyethyl thiocyanate 4 phenoxyphenoxyethyl thiocyanate antiparasitic agent atovaquone benznidazole nitro derivative thiocyanic acid derivative unclassified drug antiproliferative activity article biological activity Chagas disease controlled study drug cytotoxicity drug design drug screening drug synthesis nonhuman tachyzoite Toxoplasma gondii toxoplasmosis Trypanosoma cruzi Antiparasitic agents Chagas disease Squalene synthase inhibitors Toxoplasma gondii Toxoplasmosis Trypanosoma cruzi WC-9 analogs Antiparasitic Agents Dose-Response Relationship, Drug Drug Design Molecular Structure Parasitic Sensitivity Tests Phenyl Ethers Structure-Activity Relationship Thiocyanates Toxoplasma Trypanosoma cruzi
description	As a part of our project pointed at the search of new safe chemotherapeutic and chemoprophylactic agents against parasitic diseases, several compounds structurally related to 4-phenoxyphenoxyethyl thiocyanate (WC-9), which were modified at the terminal aromatic ring, were designed, synthesized and evaluated as antiproliferative agents against Trypanosoma cruzi, the parasite responsible of American trypanosomiasis (Chagas disease) and Toxoplasma gondii, the etiological agent of toxoplasmosis. Most of the synthetic analogs exhibited similar antiparasitic activity being slightly more potent than the reference compound WC-9. For example, the nitro derivative 13 showed an ED50 value of 5.2 μM. Interestingly, the regioisomer of WC-9, compound 36 showed similar inhibitory action than WC-9 indicating that para-phenyl substitution pattern is not necessarily required for biological activity. The biological evaluation against T. gondii was also very promising. The ED50 values corresponding for 13, 36 and 37 were at the very low micromolar level against tachyzoites of T. gondii. © 2013 Elsevier Masson SAS. All rights reserved.
author	Szajnman, Sergio Hernán Moreno, Silvia N. J. Rodríguez, Juan Bautista
author_facet	Szajnman, Sergio Hernán Moreno, Silvia N. J. Rodríguez, Juan Bautista
author_sort	Szajnman, Sergio Hernán
title	Design, synthesis and biological evaluation of WC-9 analogs as antiparasitic agents
title_short	Design, synthesis and biological evaluation of WC-9 analogs as antiparasitic agents
title_full	Design, synthesis and biological evaluation of WC-9 analogs as antiparasitic agents
title_fullStr	Design, synthesis and biological evaluation of WC-9 analogs as antiparasitic agents
title_full_unstemmed	Design, synthesis and biological evaluation of WC-9 analogs as antiparasitic agents
title_sort	design, synthesis and biological evaluation of wc-9 analogs as antiparasitic agents
publishDate	2013
url	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_02235234_v69_n_p480_Elicio http://hdl.handle.net/20.500.12110/paper_02235234_v69_n_p480_Elicio
work_keys_str_mv	AT szajnmansergiohernan designsynthesisandbiologicalevaluationofwc9analogsasantiparasiticagents AT morenosilvianj designsynthesisandbiologicalevaluationofwc9analogsasantiparasiticagents AT rodriguezjuanbautista designsynthesisandbiologicalevaluationofwc9analogsasantiparasiticagents
_version_	1840325493843296256

Design, synthesis and biological evaluation of WC-9 analogs as antiparasitic agents

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