Author | Freitas, Rosana H. C. N. | |
Author | Barbosa, Juliana M. C. | |
Author | Bernardino, Patrícia | |
Author | Sueth-Santiago, Vitor | |
Author | Wardell, Solange M. S. V. | |
Author | Wardell, James L. | |
Author | Ricardo, Debora Decote | |
Author | Melo, Tatiana G. | |
Author | Silva, Edson F. da | |
Author | Salomão, Kelly | |
Author | Fraga, Carlos A. M. | |
Access date | 2020-08-10T18:45:56Z | |
Available date | 2020-08-10T18:45:56Z | |
Document date | 2020 | |
Citation | FREITAS, Rosana H. C. N. et al. Synthesis and trypanocidal activity of novel pyridinyl-1,3,4-thiadiazole derivatives. Biomedicine & Pharmacotherapy, v. 127, 110162, p. 1-14, 2020. | pt_BR |
ISSN | 0753-3322 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/42620 | |
Language | eng | pt_BR |
Publisher | Elsevier | pt_BR |
Rights | restricted access | pt_BR |
Subject in Portuguese | Doença de Chagas | pt_BR |
Subject in Portuguese | Atividade tripocida | pt_BR |
Subject in Portuguese | Inibidor da biossíntese de esterol | pt_BR |
Subject in Portuguese | 2-amino-1,3,4-thiadiazole | pt_BR |
Subject in Portuguese | 1.3,4-thiadiazole-N-arylhydrazone | pt_BR |
Title | Synthesis and trypanocidal activity of novel pyridinyl-1,3,4-thiadiazole derivatives | pt_BR |
Type | Article | pt_BR |
DOI | 10.1016/j.biopha.2020.110162 | |
Abstract | Herein, we present the design, synthesis and trypanocidal evaluation of sixteen new 1,3,4-thiadiazole derivatives from N-aminobenzyl or N-arylhydrazone series. All derivatives were assayed against the trypomastigote form of Trypanosoma cruzi, showing IC50 values ranging from 3 to 226 μM, and a better trypanocidal profile was demonstrated for the 1,3,4-thiadiazole-N-arylhydrazones (3a-g). In this series, the 2-pyridinyl fragment bound to the imine subunit of the hydrazine moiety presented pharmacophoric behavior for trypanocidal activity. Compounds 2a, 11a and 3e presented remarkable activity and excellent selectivity indexes. Compound 2a was also active against the intracellular amastigote form of T. cruzi. Moreover, its corresponding hydrochloride, compound 11a, showed the most promising profile, producing phenotypic changes similar to those caused by posaconazole, a well-known inhibitor of sterol biosynthesis. Thus, 1,3,4-thiadiazole derivative 11a could be considered a good prototype for the development of new drug candidates for Chagas disease therapy. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Ciências Biomédicas. Laboratório de Avaliação e Síntese de Substâncias Bioativas. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Instituto Federal de Educação, Ciência e Tecnologia do Rio de Janeiro. Campus São Gonçalo. São Gonçalo, TJ, Brasil. | pt_BR |
Affilliation | CHEMSOL. Scotland, UK. | pt_BR |
Affilliation | University of Aberdeen. Department of Chemistry. Scotland, UK. | pt_BR |
Affilliation | Universidade Federal Rural do Rio de Janeiro. Instituto de Veterinária. Departamento de Microbiologia e Imunologia Veterinária. Sropédica, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Ultraestrutura Celular. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto de Tecnologia em Fármacos. Rio de Janeiro, RJ, Brasil / Universidade do Grande Rio. Escola de Ciência e Tecnologia. Duque de Caxias, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Ciências Biomédicas. Laboratório de Avaliação e Síntese de Substâncias Bioativas. Rio de Janeiro, RJ, Brasil. | pt_BR |
Subject | Chagas Disease | pt_BR |
Subject | Trypanocidal activity | pt_BR |
Subject | Inhibitor of sterol biosynthesis | pt_BR |
Subject | 2-amino-1,3,4-thiadiazole | pt_BR |
Subject | 1,3,4-thiadiazole-N-arylhydrazone | pt_BR |
Embargo date | 2022-01-01 | |