Author | Santos Filho, José Maurício dos | |
Author | Leite, Ana Cristina Lima | |
Author | Oliveira, Boaz Galdino de | |
Author | Moreira, Diogo Rodrigo Magalhães | |
Author | Lima, Milena da Silva | |
Author | Soares, Milena Botelho Pereira | |
Author | Leite, Lucia Fernanda Cavalcanti da Costa | |
Access date | 2014-12-01T18:55:39Z | |
Available date | 2014-12-01T18:55:39Z | |
Document date | 2009 | |
Citation | SANTOS FILHO, J. M. dos Design, synthesis and cruzain docking of 3-(4-substituted-aryl)-1,2,4-oxadiazole-N-acylhydrazones as anti-Trypanosoma cruzi agents. Bioorganic & Medicinal Chemistry, v. 17, n. 18, p. 6682-6691, 2009. | pt_BR |
ISSN | 1464-3391 | |
URI | https://www.arca.fiocruz.br/handle/icict/9021 | |
Language | eng | pt_BR |
Publisher | Elsevier Ltd | pt_BR |
Rights | open access | pt_BR |
Title | Design, synthesis and cruzain docking of 3-(4-substituted-aryl)-1,2,4-oxadiazole-N-acylhydrazones as anti-Trypanosoma cruzi agents | pt_BR |
Type | Article | pt_BR |
DOI | 10.1016/j.bmc.2009.07.068 | |
Abstract | Research in recent years has demonstrated that the Trypanosoma cruzi cysteine protease cruzain (TCC) is a
valid chemotherapeutic target, since inhibitors of this protease affect the pathology appropriately. By
exploring the N-acylhydrazones (NAH) as privileged structures usually present in antiparasitic agents,
we investigated a library of 16 NAH bearing the 3-(4-substituted-aryl)-1,2,4-oxadiazole scaffold (NAH
3a–h, 4a–h). The in vitro bioactivity against epimastigote and trypomastigote forms of T. cruzi was evaluated,
and some NAH under study exhibited antitrypanosomal activity at concentrations that are not
toxic to mammalian cells. The series of compounds based on the 3-(4-substituted-aryl)-1,2,4-oxadiazole
scaffold revealed the remarkable importance of each substituent at the phenyl’s 4-position for the inhibitory
activity. Non-nitrated compounds 3a and 4e were found to be as potent as the reference drug, Benznidazole.
In addition, the molecular origin of the antitrypanosomal properties for these series was
investigated using docking studies of the TCC structure. | pt_BR |
Affilliation | Universidade Federal de Pernambuco. Departamento de Engenharia Química. Centro de Tecnologia e Geociências. Recife, PE, Brasil | pt_BR |
Affilliation | Universidade Federal de Pernambuco. Departamento de Ciências Farmacêuticas. Centro de Ciências da Saúde. Recife, PE, Brasil | pt_BR |
Affilliation | Universidade Federal de Pernambuco. Departamento de Ciências Farmacêuticas. Centro de Ciências da Saúde. Recife, PE, Brasil | pt_BR |
Affilliation | Universidade Federal de Pernambuco. Departamento de Ciências Farmacêuticas. Centro de Ciências da Saúde. Recife, PE, Brasil | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Salvador, BA, Brasil | pt_BR |
Affilliation | Universidade Católica de Pernambuco. UNICAP. Recife, PE, Brasil | pt_BR |
Subject | Trypanosoma cruzi | pt_BR |
Subject | Oxadiazole | pt_BR |
Subject | Oxadiazole | pt_BR |
Subject | Privileged structures | pt_BR |
Subject | Molecular docking | pt_BR |
Subject | Cruzain | pt_BR |
DeCS | Doença de Chagas/quimioterapia | pt_BR |
DeCS | Cisteína Endopeptidases/metabolismo | pt_BR |
DeCS | Hidrazonas/farmacologia | pt_BR |
DeCS | Oxidiazóis/farmacologia | pt_BR |
DeCS | Proteínas de Protozoários/metabolismo | pt_BR |
DeCS | Tripanossomicidas/farmacologia | pt_BR |
DeCS | Trypanosoma cruzi/efeitos de drogas | pt_BR |
DeCS | Animais | pt_BR |
DeCS | Sobrevivência Celular/efeitos de drogas | pt_BR |
DeCS | Hidrazonas/administração & dosagem | pt_BR |
DeCS | Camundongos | pt_BR |
DeCS | Camundongos Endogâmicos BALB C | pt_BR |
DeCS | Modelos Moleculares | pt_BR |
DeCS | Oxidiazóis/administração & dosagem | pt_BR |
DeCS | Testes de Sensibilidade Parasitária | pt_BR |
DeCS | Ligação Proteica | pt_BR |
DeCS | Proteínas de Protozoários/química | pt_BR |
DeCS | Baço/citologia | pt_BR |
DeCS | Relação Estrutura-Atividade | pt_BR |
DeCS | Tripanossomicidas/administração & dosagem | pt_BR |
DeCS | Trypanosoma cruzi/metabolismo | pt_BR |