Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/9021
Title: Design, synthesis and cruzain docking of 3-(4-substituted-aryl)-1,2,4-oxadiazole-N-acylhydrazones as anti-Trypanosoma cruzi agents
Authors: Santos Filho, José Maurício dos
Leite, Ana Cristina Lima
Oliveira, Boaz Galdino de
Moreira, Diogo Rodrigo Magalhães
Lima, Milena da Silva
Soares, Milena Botelho Pereira
Leite, Lucia Fernanda Cavalcanti da Costa
Affilliation: Universidade Federal de Pernambuco. Departamento de Engenharia Química. Centro de Tecnologia e Geociências. Recife, PE, Brasil
Universidade Federal de Pernambuco. Departamento de Ciências Farmacêuticas. Centro de Ciências da Saúde. Recife, PE, Brasil
Universidade Federal de Pernambuco. Departamento de Ciências Farmacêuticas. Centro de Ciências da Saúde. Recife, PE, Brasil
Universidade Federal de Pernambuco. Departamento de Ciências Farmacêuticas. Centro de Ciências da Saúde. Recife, PE, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Salvador, BA, Brasil
Universidade Católica de Pernambuco. UNICAP. Recife, PE, Brasil
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.
Keywords: Trypanosoma cruzi
Oxadiazole
Oxadiazole
Privileged structures
Molecular docking
Cruzain
DeCS: Doença de Chagas/quimioterapia
Cisteína Endopeptidases/metabolismo
Hidrazonas/farmacologia
Oxidiazóis/farmacologia
Proteínas de Protozoários/metabolismo
Tripanossomicidas/farmacologia
Trypanosoma cruzi/efeitos de drogas
Animais
Sobrevivência Celular/efeitos de drogas
Hidrazonas/administração & dosagem
Camundongos
Camundongos Endogâmicos BALB C
Modelos Moleculares
Oxidiazóis/administração & dosagem
Testes de Sensibilidade Parasitária
Ligação Proteica
Proteínas de Protozoários/química
Baço/citologia
Relação Estrutura-Atividade
Tripanossomicidas/administração & dosagem
Trypanosoma cruzi/metabolismo
Issue Date: 2009
Publisher: Elsevier Ltd
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.
DOI: 10.1016/j.bmc.2009.07.068
ISSN: 1464-3391
Copyright: open access
Appears in Collections:BA - IGM - Artigos de Periódicos

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