| Author | Fonseca, Nayara Cristina | |
| Author | Cruz, Luana Faria da | |
| Author | Villela, Filipe da Silva | |
| Author | Pereira, Glaécia Aparecida do Nascimento | |
| Author | Siqueira Neto, Jair Lage de | |
| Author | Kellar, Danielle | |
| Author | Suzuki, Brian M. | |
| Author | Ray, Debalina | |
| Author | Souza, Thiago Belarmino de | |
| Author | Alves, Ricardo José | |
| Author | Sales Júnior, Policarpo Ademar | |
| Author | Romanha, Alvaro José | |
| Author | Murta, Silvane Maria Fonseca | |
| Author | McKerrow, James H. | |
| Author | Caffrey, Conor R. | |
| Author | Oliveira, Renata Barbosa de | |
| Author | Ferreira, Rafaela Salgado | |
| Access date | 2016-01-28T12:38:57Z | |
| Available date | 2016-01-28T12:38:57Z | |
| Document date | 2015 | |
| Citation | FONSECA, Nayara Cristina et al. Synthesis of a sugar-based thiosemicarbazone series and structure-activity relationship versus the parasite cysteine proteases: rhodesain; cruzain and Schistosoma mansoni cathepsin B1. Antimicrob Agents Chemother., Vol. 59n. 5, p. 2666–2677, 2015. | pt_BR |
| ISSN | 0066-4804 | |
| URI | https://www.arca.fiocruz.br/handle/icict/12640 | |
| Language | eng | pt_BR |
| Publisher | American Society for Microbiology | pt_BR |
| Rights | open access | pt_BR |
| Title | Synthesis of a sugar-based thiosemicarbazone series and structure-activity relationship versus the parasite cysteine proteases: rhodesain; cruzain and Schistosoma mansoni cathepsin B1 | pt_BR |
| Type | Article | pt_BR |
| DOI | 10.1128/AAC.04601-14 | |
| Abstract | The pressing need for better drugs against Chagas disease, African sleeping sickness, and schistosomiasis motivates the search for inhibitors of cruzain, rhodesain, and Schistosoma mansoni CB1 (SmCB1), the major cysteine proteases from Trypanosoma cruzi, Trypanosoma brucei, and S. mansoni, respectively. Thiosemicarbazones and heterocyclic analogues have been shown to be both antitrypanocidal and inhibitory against parasite cysteine proteases. A series of compounds was synthesized and evaluated against cruzain, rhodesain, and SmCB1 through biochemical assays to determine their potency and structure-activity relationships (SAR). This approach led to the discovery of 6 rhodesain, 4 cruzain, and 5 SmCB1 inhibitors with 50% inhibitory concentrations (IC50s) of ≤ 10 μM. Among the compounds tested, the thiosemicarbazone derivative of peracetylated galactoside (compound 4i) was discovered to be a potent rhodesain inhibitor (IC50 = 1.2 ± 1.0 μM). The impact of a range of modifications was determined; removal of thiosemicarbazone or its replacement by semicarbazone resulted in virtually inactive compounds, and modifications in the sugar also diminished potency. Compounds were also evaluated in vitro against the parasites T. cruzi, T. brucei, and S. mansoni, revealing active compounds among this series. | pt_BR |
| Affilliation | Universidade Federal de Minas Gerais. Faculdade de Farmácia. Departamento de Produtos Farmacêuticos. Belo Horizonte, MG, Brasil | pt_BR |
| Affilliation | Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brasil | pt_BR |
| Affilliation | Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brasil | pt_BR |
| Affilliation | Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brasil/Ministerio da Educação. Coordenação de Aperfeiçoamento de Pessoal de Nível Superior. Brasília, DF, Brasil | pt_BR |
| Affilliation | University of California. Skaggs School of Pharmacy and Pharmaceutical Sciences. San Diego, CA, USA | pt_BR |
| Affilliation | University of California. Center for Discovery and Innovation in Parasitic Diseases and Department of Pathology. San Francisco, CA, USA | pt_BR |
| Affilliation | University of California. Center for Discovery and Innovation in Parasitic Diseases and Department of Pathology. San Francisco, CA, USA | pt_BR |
| Affilliation | University of California. Center for Discovery and Innovation in Parasitic Diseases and Department of Pathology. San Francisco, CA, USA | pt_BR |
| Affilliation | Universidade Federal de Minas Gerais. Faculdade de Farmácia. Departamento de Produtos Farmacêuticos. Belo Horizonte, MG, Brasil | pt_BR |
| Affilliation | Universidade Federal de Minas Gerais. Faculdade de Farmácia. Departamento de Produtos Farmacêuticos. Belo Horizonte, MG, Brasil | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brasil | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brasil/Universidade Federal de Santa Catarina. Departamento de Microbiologia, Imunologia e Parasitologia. Florianópolis, SC, Brasil | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brasil | pt_BR |
| Affilliation | University of California. Skaggs School of Pharmacy and Pharmaceutical Sciences. San Diego, CA, USA | pt_BR |
| Affilliation | University of California. Center for Discovery and Innovation in Parasitic Diseases and Department of Pathology. San Francisco, CA, USA | pt_BR |
| Affilliation | Universidade Federal de Minas Gerais. Faculdade de Farmácia. Departamento de Produtos Farmacêuticos. Belo Horizonte, MG, Brasil | pt_BR |
| Affilliation | Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brasil | pt_BR |
| Subject | Cathepsin B/metabolism | pt_BR |
| Subject | Cysteine Proteinase | pt_BR |
| Subject | Inhibitors/chemical synthesis | pt_BR |
| Subject | Cysteine Proteinase | pt_BR |
| Subject | Inhibitors/pharmacology | pt_BR |
| Subject | Trypanocidal Agents/chemical synthesis | pt_BR |
