Author | Hernandes, Marcelo Zaldini | |
Author | Rabello, Marcelo Montenegro | |
Author | Leite, Ana Cristina Lima | |
Author | Cardoso, Marcos Veríssimo Oliveira | |
Author | Moreira, Diogo Rodrigo Magalhaes | |
Author | Brondani, Dalci José | |
Author | Simone, Carlos Alberto | |
Author | Reis, Luiza Campos | |
Author | Souza, Marina Assis | |
Author | Pereira, Valéria Rego Alves | |
Author | Ferreira, Rafaela Salgado | |
Author | McKerrow, James Hobson | |
Access date | 2018-08-14T13:21:42Z | |
Available date | 2018-08-14T13:21:42Z | |
Document date | 2010 | |
Citation | HERNANDES, M. Z. et al. Studies toward the structural optimization of novel thiazolylhydrazone-based potent antitrypanosomal agents. Bioorganic & Medicinal Chemistry, v. 18, n. 22, p. 7826–7835, 15 nov. 2010. | pt_BR |
ISSN | 1464-3391 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/28122 | |
Sponsorship | Esta pesquisa recebeu apoio da Fundação Estadual de Ciência e Tecnologia de Pernambuco (FACEPE, outorga nº APQ-0123-4.03 / 08 ) e do Conselho Nacional de Pesquisa (CNPq, outorga nº 472880 / 2009-8 ). | pt_BR |
Language | eng | pt_BR |
Publisher | Elsevier | pt_BR |
Rights | restricted access | pt_BR |
Subject in Portuguese | Bioisosterismo | pt_BR |
Subject in Portuguese | Cisteína protease cruzain | pt_BR |
Subject in Portuguese | Hidrazonas | pt_BR |
Subject in Portuguese | Ancoragem Molecular | pt_BR |
Subject in Portuguese | Tiazoles | pt_BR |
Subject in Portuguese | Tiossemicarbazonas | pt_BR |
Subject in Portuguese | Trypanosoma cruzi | pt_BR |
Title | Studies toward the structural optimization of novel thiazolylhydrazone-based potent antitrypanosomal agents | pt_BR |
Type | Article | pt_BR |
DOI | 10.1016/j.bmc.2010.09.056 | |
Abstract | In previous studies, we identified promising anti-Trypanosoma cruzi cruzain inhibitors based on thiazolylhydrazones. To optimize this series, a number of medicinal chemistry directions were explored and new thiazolylhydrazones and thiosemicarbazones were thus synthesized. Potent cruzain inhibitors were identified, such as thiazolylhydrazones 3b and 3j, which exhibited IC(50) of 200-400nM. Furthermore, molecular docking studies showed concordance with experimentally derived structure-activity relationships (SAR) data. In the course of this work, lead compounds exhibiting in vitro activity against both the epimastigote and trypomastigote forms of T. cruzi were identified and in vivo general toxicity analysis was subsequently performed. Novel SAR were documented, including the importance of the thiocarbonyl carbon attached to the thiazolyl ring and the direct comparison between thiosemicarbazones and thiazolylhydrazones. | pt_BR |
Affilliation | Federal University of Pernambuco. Centre for Health Science. Department of Pharmaceutical Sciences. Recife, PE, Brazil. | pt_BR |
Affilliation | Federal University of Pernambuco. Centre for Health Science. Department of Pharmaceutical Sciences. Recife, PE, Brazil. | pt_BR |
Affilliation | Federal University of Pernambuco. Centre for Health Science. Department of Pharmaceutical Sciences. Recife, PE, Brazil. | pt_BR |
Affilliation | Federal University of Pernambuco. Centre for Health Science. Department of Pharmaceutical Sciences. Recife, PE, Brazil. | pt_BR |
Affilliation | Federal University of Pernambuco. Centre for Health Science. Department of Pharmaceutical Sciences. Recife, PE, Brazil. | pt_BR |
Affilliation | Federal University of Pernambuco. Centre for Health Science. Department of Pharmaceutical Sciences. Recife, PE, Brazil. | pt_BR |
Affilliation | University of São Paulo. Institute of Physics. Department of Physics and Informatics. São Carlos, SP, Brazil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Departamento de Imunologia. Recife, PE, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Departamento de Imunologia. Recife, PE, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Departamento de Imunologia. Recife, PE, Brasil. | pt_BR |
Affilliation | University of California. Sandler Center for Drug Discovery in Parasitic Diseases. San Francisco, CA, USA. | pt_BR |
Affilliation | University of California. Sandler Center for Drug Discovery in Parasitic Diseases. San Francisco, CA, USA. | pt_BR |
Subject | Bioisosterism | pt_BR |
Subject | Cysteine protease cruzain | pt_BR |
Subject | Hydrazones | pt_BR |
Subject | Molecular docking | pt_BR |
Subject | Thiazoles | pt_BR |
Subject | Thiosemicarbazones | pt_BR |
Subject | Trypanosoma cruzi | pt_BR |
DeCS | Animais | pt_BR |
DeCS | Encadernação | pt_BR |
DeCS | Células Cultivadas | pt_BR |
DeCS | Simulação de computador | pt_BR |
DeCS | Cisteína Proteases / química | pt_BR |
DeCS | Proteases de cisteína / metabolismo | pt_BR |
DeCS | Inibidores da Proteína Cisteína / síntese química | pt_BR |
DeCS | Inibidores da Proteína Cisteína / química | pt_BR |
DeCS | Inibidores da Proteína Cisteína / toxicidade | pt_BR |
DeCS | Fêmea | pt_BR |
DeCS | Hidrazonas / síntese química | pt_BR |
DeCS | Hidrazonas / química | pt_BR |
DeCS | Hidrazonas / toxicidade | pt_BR |
DeCS | Ratos | pt_BR |
DeCS | Estrutura proteica, terciária | pt_BR |
DeCS | Estereoisomerismo | pt_BR |
DeCS | Relação Estrutura-Atividade | pt_BR |
DeCS | Triazoles / química | pt_BR |
DeCS | Agentes Tripanocidas / síntese química | pt_BR |
DeCS | Agentes Tripanocidas / Química | pt_BR |
DeCS | Agentes Tripanocidas / toxicidade | pt_BR |
DeCS | Trypanosoma cruzi / efeitos de drogas | pt_BR |
Embargo date | 2050-01-01 | |