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https://www.arca.fiocruz.br/handle/icict/25583
EVALUATION OF THE ANTI-SCHISTOSOMA MANSONI ACTIVITY OF THIOSEMICARBAZONES AND THIAZOLES
Esquistossomicidas
Praziquantel
Tiazóis
Quimioterapia
Droga
Author
Santiago, Edna de Farias
Oliveira, Sheilla Andrade de
Oliveira Filho, Gevânio Bezerra de
Moreira, Diogo Rodrigo Magalhaes
Gomes, Paulo André Teixeira
Silva, Anekécia Lauro da
Barros, Andréia Ferreira de
Silva, Aline Caroline da
Santos, Thiago André Ramos dos
Pereira, Valéria Rêgo Alves
Gonçalves, Gabriel Gazzoni Araújo
Brayner, Fábio André
Alves, Luiz Carlos
Wanderley, Almir Gonçalves
Leite, Ana Cristina Lima
Oliveira, Sheilla Andrade de
Oliveira Filho, Gevânio Bezerra de
Moreira, Diogo Rodrigo Magalhaes
Gomes, Paulo André Teixeira
Silva, Anekécia Lauro da
Barros, Andréia Ferreira de
Silva, Aline Caroline da
Santos, Thiago André Ramos dos
Pereira, Valéria Rêgo Alves
Gonçalves, Gabriel Gazzoni Araújo
Brayner, Fábio André
Alves, Luiz Carlos
Wanderley, Almir Gonçalves
Leite, Ana Cristina Lima
Affilliation
Federal University of Pernambuco. Department of Pharmacy. Recife, PE, Brazil / Federal University of Pernambuco. Laboratory of Immunopathology. Recife, PE, Brazil
Federal University of Pernambuco. Laboratory of Immunopathology. Recife, PE, Brazil
Federal University of Pernambuco. Department of Pharmacy. Recife, PE, Brazil
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil
Federal University of Pernambuco. Department of Pharmacy. Recife, PE, Brazil
Federal University of Pernambuco. Laboratory of Immunopathology. Recife, PE, Brazil
Federal University of Pernambuco. Laboratory of Immunopathology. Recife, PE, Brazil
Federal University of Pernambuco. Laboratory of Immunogenetics. Recife, PE, Brazil
Federal University of Pernambuco. Laboratory of Immunogenetics. Recife, PE, Brazil
Federal University of Pernambuco. Laboratory of Immunogenetics. Recife, PE, Brazil
Fundação Oswaldo Cruz. Centro de Pesquisas Aggeu Magalhães. Recife, PE, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas Aggeu Magalhães. Recife, PE, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas Aggeu Magalhães. Recife, PE, Brasil
Federal University of Pernambuco. Department of Physiology and Pharmacology. Recife, PE, Brazil
Federal University of Pernambuco. Department of Pharmacy. Recife, PE, Brazil
Federal University of Pernambuco. Laboratory of Immunopathology. Recife, PE, Brazil
Federal University of Pernambuco. Department of Pharmacy. Recife, PE, Brazil
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil
Federal University of Pernambuco. Department of Pharmacy. Recife, PE, Brazil
Federal University of Pernambuco. Laboratory of Immunopathology. Recife, PE, Brazil
Federal University of Pernambuco. Laboratory of Immunopathology. Recife, PE, Brazil
Federal University of Pernambuco. Laboratory of Immunogenetics. Recife, PE, Brazil
Federal University of Pernambuco. Laboratory of Immunogenetics. Recife, PE, Brazil
Federal University of Pernambuco. Laboratory of Immunogenetics. Recife, PE, Brazil
Fundação Oswaldo Cruz. Centro de Pesquisas Aggeu Magalhães. Recife, PE, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas Aggeu Magalhães. Recife, PE, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas Aggeu Magalhães. Recife, PE, Brasil
Federal University of Pernambuco. Department of Physiology and Pharmacology. Recife, PE, Brazil
Federal University of Pernambuco. Department of Pharmacy. Recife, PE, Brazil
Abstract
Schistosomiasis is a chronic and debilitating disease caused by a trematode of the genus Schistosoma and affects over 207 million people. Chemotherapy is the only immediate recourse for minimizing the prevalence of this disease and involves predominately the administration of a single drug, praziquantel (PZQ). Although PZQ has proven efficacy, there is a recognized need to develop new drugs as schistosomicides since studies have shown that repeated use of this drug in areas of endemicity may cause a temporary reduction in susceptibility in isolates of Schistosoma mansoni. Hydrazones, thiosemicarbazones, phthalimides, and thiazoles are thus regarded as privileged structures used for a broad spectrum of activities and are potential candidates for sources of new drug prototypes. The present study determined the in vitro schistosomicidal activity of 10 molecules containing these structures. During the assays, parameters such motility and mortality, oviposition, morphological changes in the tegument, cytotoxicity, and immunomodulatory activity caused by these compounds were evaluated. The results showed that compounds formed of thiazole and phthalimide led to higher mortality of worms, with a significant decline in motility, inhibition of pairing and oviposition, and a mortality rate of 100% starting from 144 h of exposure. These compounds also stimulated the production of nitric oxide and tumor necrosis factor alpha (TNF-α), thereby demonstrating the presence of immunomodulatory activity. The phthalyl thiazole LpQM-45 caused significant ultrastructural alterations, with destruction of the tegument in both male and female worms. According to the present study, phthalyl thiazole compounds possess antischistosomal activities and should form the basis for future experimental and clinical trials.
Keywords in Portuguese
Schistosoma mansoniEsquistossomicidas
Praziquantel
Tiazóis
Quimioterapia
Droga
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