Structure-activity relationship of new growth inhibitors of Trypanosoma cruzi

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Several drugs bearing the 4-phenoxyphenoxy skeleton and other closely related structures were designed, synthesized, and evaluated as antiproliferative agents against Trypanosoma cruzi, the etiologic agent of Chagas' disease. The new class of drugs was envisioned by modifying the nonpolar 4-phe...

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Autores principales: Cinque, G.M., Szajnman, S.H., Zhong, L., Docampo, R., Schvartzapel, A.J., Rodriguez, J.B., Gros, E.G.
Formato: JOUR
Materias:
4 phenoxyphenoxyethyl thiocyanate
nifurtimox
unclassified drug
article
chagas disease
drug screening
drug structure
drug synthesis
epimastigote
trypanosoma cruzi
Animals
Drug Evaluation, Preclinical
Nifurtimox
Phenyl Ethers
Structure-Activity Relationship
Thiocyanates
Trypanocidal Agents
Trypanosoma cruzi
Acceso en línea:http://hdl.handle.net/20.500.12110/paper_00222623_v41_n9_p1540_Cinque
Aporte de:
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires
id todo:paper_00222623_v41_n9_p1540_Cinque
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spelling todo:paper_00222623_v41_n9_p1540_Cinque2023-10-03T14:30:13Z Structure-activity relationship of new growth inhibitors of Trypanosoma cruzi Cinque, G.M. Szajnman, S.H. Zhong, L. Docampo, R. Schvartzapel, A.J. Rodriguez, J.B. Gros, E.G. 4 phenoxyphenoxyethyl thiocyanate nifurtimox unclassified drug article chagas disease drug screening drug structure drug synthesis epimastigote trypanosoma cruzi Animals Drug Evaluation, Preclinical Nifurtimox Phenyl Ethers Structure-Activity Relationship Thiocyanates Trypanocidal Agents Trypanosoma cruzi Several drugs bearing the 4-phenoxyphenoxy skeleton and other closely related structures were designed, synthesized, and evaluated as antiproliferative agents against Trypanosoma cruzi, the etiologic agent of Chagas' disease. The new class of drugs was envisioned by modifying the nonpolar 4-phenoxyphenoxy moiety replacing selected aromatic protons by different groups via electrophilic aromatic substitution reactions as well as introducing a sulfur atom at file polar extreme. Of the designed compounds, sulfur-containing derivatives were shown to be potent antireplicative agents against T. cruzi. Among these drugs, 4-phenoxyphenoxyethyl thiocyanate (compound 56) proved to be an extremely active growth inhibitor of the epimastigote forms of T. cruzi and displayed an IC500 of 2.2 μM. Under the same assay conditions, this drug was much more active than Nifurtimox, one of the drugs currently in clinical use to control this disease. This thiocyanate derivative was also a very active inhibitor against the intracellular form of the parasite at the nanomolar level. Other sulfur derivatives prepared also exhibited very potent antiproliferative action against T. cruzi. The presence of a sulfur atom at the polar extreme for this family of compounds seems to be very important for biological action because this atom was always associated with high inhibition values. 4-Phenoxyphenoxyethyl thiocyanate presents very good prospective not only as a lead drug but also as a potential chemotherapeutic agent. Fil:Szajnman, S.H. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Schvartzapel, A.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. Fil:Gros, E.G. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00222623_v41_n9_p1540_Cinque
institution Universidad de Buenos Aires
institution_str I-28
repository_str R-134
collection Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic 4 phenoxyphenoxyethyl thiocyanate
nifurtimox
unclassified drug
article
chagas disease
drug screening
drug structure
drug synthesis
epimastigote
trypanosoma cruzi
Animals
Drug Evaluation, Preclinical
Nifurtimox
Phenyl Ethers
Structure-Activity Relationship
Thiocyanates
Trypanocidal Agents
Trypanosoma cruzi
spellingShingle 4 phenoxyphenoxyethyl thiocyanate
nifurtimox
unclassified drug
article
chagas disease
drug screening
drug structure
drug synthesis
epimastigote
trypanosoma cruzi
Animals
Drug Evaluation, Preclinical
Nifurtimox
Phenyl Ethers
Structure-Activity Relationship
Thiocyanates
Trypanocidal Agents
Trypanosoma cruzi
Cinque, G.M.
Szajnman, S.H.
Zhong, L.
Docampo, R.
Schvartzapel, A.J.
Rodriguez, J.B.
Gros, E.G.
Structure-activity relationship of new growth inhibitors of Trypanosoma cruzi
topic_facet 4 phenoxyphenoxyethyl thiocyanate
nifurtimox
unclassified drug
article
chagas disease
drug screening
drug structure
drug synthesis
epimastigote
trypanosoma cruzi
Animals
Drug Evaluation, Preclinical
Nifurtimox
Phenyl Ethers
Structure-Activity Relationship
Thiocyanates
Trypanocidal Agents
Trypanosoma cruzi
description Several drugs bearing the 4-phenoxyphenoxy skeleton and other closely related structures were designed, synthesized, and evaluated as antiproliferative agents against Trypanosoma cruzi, the etiologic agent of Chagas' disease. The new class of drugs was envisioned by modifying the nonpolar 4-phenoxyphenoxy moiety replacing selected aromatic protons by different groups via electrophilic aromatic substitution reactions as well as introducing a sulfur atom at file polar extreme. Of the designed compounds, sulfur-containing derivatives were shown to be potent antireplicative agents against T. cruzi. Among these drugs, 4-phenoxyphenoxyethyl thiocyanate (compound 56) proved to be an extremely active growth inhibitor of the epimastigote forms of T. cruzi and displayed an IC500 of 2.2 μM. Under the same assay conditions, this drug was much more active than Nifurtimox, one of the drugs currently in clinical use to control this disease. This thiocyanate derivative was also a very active inhibitor against the intracellular form of the parasite at the nanomolar level. Other sulfur derivatives prepared also exhibited very potent antiproliferative action against T. cruzi. The presence of a sulfur atom at the polar extreme for this family of compounds seems to be very important for biological action because this atom was always associated with high inhibition values. 4-Phenoxyphenoxyethyl thiocyanate presents very good prospective not only as a lead drug but also as a potential chemotherapeutic agent.
format JOUR
author Cinque, G.M.
Szajnman, S.H.
Zhong, L.
Docampo, R.
Schvartzapel, A.J.
Rodriguez, J.B.
Gros, E.G.
author_facet Cinque, G.M.
Szajnman, S.H.
Zhong, L.
Docampo, R.
Schvartzapel, A.J.
Rodriguez, J.B.
Gros, E.G.
author_sort Cinque, G.M.
title Structure-activity relationship of new growth inhibitors of Trypanosoma cruzi
title_short Structure-activity relationship of new growth inhibitors of Trypanosoma cruzi
title_full Structure-activity relationship of new growth inhibitors of Trypanosoma cruzi
title_fullStr Structure-activity relationship of new growth inhibitors of Trypanosoma cruzi
title_full_unstemmed Structure-activity relationship of new growth inhibitors of Trypanosoma cruzi
title_sort structure-activity relationship of new growth inhibitors of trypanosoma cruzi
url http://hdl.handle.net/20.500.12110/paper_00222623_v41_n9_p1540_Cinque
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