Structure-activity relationship of new growth inhibitors of 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-phe...
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1998
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paper:paper_00222623_v41_n9_p1540_Cinque2023-06-08T14:48:35Z Structure-activity relationship of new growth inhibitors of Trypanosoma cruzi Szajnman, Sergio Hernán Schvartzapel, Andrea Judith Rodríguez, Juan Bautista Gros, Eduardo Gervasio 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. 1998 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00222623_v41_n9_p1540_Cinque 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 Szajnman, Sergio Hernán Schvartzapel, Andrea Judith Rodríguez, Juan Bautista Gros, Eduardo Gervasio 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. |
| author |
Szajnman, Sergio Hernán Schvartzapel, Andrea Judith Rodríguez, Juan Bautista Gros, Eduardo Gervasio |
| author_facet |
Szajnman, Sergio Hernán Schvartzapel, Andrea Judith Rodríguez, Juan Bautista Gros, Eduardo Gervasio |
| author_sort |
Szajnman, Sergio Hernán |
| 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 |
| publishDate |
1998 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00222623_v41_n9_p1540_Cinque http://hdl.handle.net/20.500.12110/paper_00222623_v41_n9_p1540_Cinque |
| work_keys_str_mv |
AT szajnmansergiohernan structureactivityrelationshipofnewgrowthinhibitorsoftrypanosomacruzi AT schvartzapelandreajudith structureactivityrelationshipofnewgrowthinhibitorsoftrypanosomacruzi AT rodriguezjuanbautista structureactivityrelationshipofnewgrowthinhibitorsoftrypanosomacruzi AT groseduardogervasio structureactivityrelationshipofnewgrowthinhibitorsoftrypanosomacruzi |
| _version_ |
1768541784548311040 |