Please use this identifier to cite or link to this item:
https://www.arca.fiocruz.br/handle/icict/33115
Type
ArticleCopyright
Restricted access
Embargo date
2050-01-01
Collections
Metadata
Show full item record34
CITATIONS
34
Total citations
11
Recent citations
3.55
Field Citation Ratio
1.84
Relative Citation Ratio
NEW 1,3-BENZODIOXOLE DERIVATIVES: SYNTHESIS, EVALUATION OF IN VITRO SCHISTOSOMICIDAL ACTIVITY AND ULTRASTRUCTURAL ANALYSIS
Sobrevivência Celular / efeitos de drogas
Dioxoles / química
Dioxoles / farmacologia
Dioxoles / uso terapêutico
Células HeLa
Humanos
Microscopia, elétron, varredura
Praziquantel / farmacologia
Praziquantel / uso terapêutico
Schistosoma mansoni / efeitos de drogas
Schistosoma mansoni / ultraestrutura
Esquistossomose / quimioterapia
Esquistossomose / patologia
Esquistossomicidas / síntese química
Esquistossomicidas / farmacologia
Esquistossomicidas / uso terapêutico
Author
Silva, Luana Maria Mariz Gomes da
Oliveira, Jamerson Ferreira de
Silva, Willams Leal
Silva, Anekecia Lauro da
Almeida Junior, Antônio Sérgio Alves de
Santos, Victor Hugo Barbosa dos
Alves, Luiz Carlos
Santos, Fábio André Brayner dos
Costa, Vlaudia Maria Assis
Aires, André de Lima
Lima, Maria do Carmo Alves de
Albuquerque, Monica Camelo Pessoa de Azevedo
Oliveira, Jamerson Ferreira de
Silva, Willams Leal
Silva, Anekecia Lauro da
Almeida Junior, Antônio Sérgio Alves de
Santos, Victor Hugo Barbosa dos
Alves, Luiz Carlos
Santos, Fábio André Brayner dos
Costa, Vlaudia Maria Assis
Aires, André de Lima
Lima, Maria do Carmo Alves de
Albuquerque, Monica Camelo Pessoa de Azevedo
Affilliation
Federal University of Pernambuco. Keizo Asami Immunopathology Laboratory. Recife, PE, Brazil.
Federal University of Pernambuco. Chemistry Laboratory and Therapeutic Inovation. Recife, PE, Brazil.
Federal University of Pernambuco. Chemistry Laboratory and Therapeutic Inovation. Recife, PE, Brazil.
Federal University of Pernambuco. Chemistry Laboratory and Therapeutic Inovation. Recife, PE, Brazil.
Federal University of Pernambuco. Chemistry Laboratory and Therapeutic Inovation. Recife, PE, Brazil.
Federal University of Pernambuco. Keizo Asami Immunopathology Laboratory. Recife, PE, Brazil.
Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, Brasil. / Federal University of Pernambuco. Keizo Asami Immunopathology Laboratory. Recife, PE, Brazil.
Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, Brasil. / Federal University of Pernambuco. Keizo Asami Immunopathology Laboratory. Recife, PE, Brazil.
Federal University of Pernambuco. Department of Tropical Medicine. Recife, PE, Brazil.
Federal University of Pernambuco. Keizo Asami Immunopathology Laboratory. Recife, PE, Brazil.
Federal University of Pernambuco. Chemistry Laboratory and Therapeutic Inovation. Recife, PE, Brazil.
Federal University of Pernambuco. Keizo Asami Immunopathology Laboratory. Recife, PE, Brazil.
Federal University of Pernambuco. Chemistry Laboratory and Therapeutic Inovation. Recife, PE, Brazil.
Federal University of Pernambuco. Chemistry Laboratory and Therapeutic Inovation. Recife, PE, Brazil.
Federal University of Pernambuco. Chemistry Laboratory and Therapeutic Inovation. Recife, PE, Brazil.
Federal University of Pernambuco. Chemistry Laboratory and Therapeutic Inovation. Recife, PE, Brazil.
Federal University of Pernambuco. Keizo Asami Immunopathology Laboratory. Recife, PE, Brazil.
Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, Brasil. / Federal University of Pernambuco. Keizo Asami Immunopathology Laboratory. Recife, PE, Brazil.
Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, Brasil. / Federal University of Pernambuco. Keizo Asami Immunopathology Laboratory. Recife, PE, Brazil.
Federal University of Pernambuco. Department of Tropical Medicine. Recife, PE, Brazil.
Federal University of Pernambuco. Keizo Asami Immunopathology Laboratory. Recife, PE, Brazil.
Federal University of Pernambuco. Chemistry Laboratory and Therapeutic Inovation. Recife, PE, Brazil.
Federal University of Pernambuco. Keizo Asami Immunopathology Laboratory. Recife, PE, Brazil.
Abstract
Schistosomiasis is considered a serious public health problem in 78 countries and territories located in Africa, Asia and America and it is estimated in more than 249 million people infected by any of the species of Schistosoma. The exclusive use of praziquantel (PZQ), effective drug against all species of Schistosoma, has been the basis of the development of a possible resistance against the strains of this parasite. In addition, PZQ is not effective against young forms of worms. Thus, there is a need for the development of new drugs with schistosomicidal activity. The objective of this work was to synthesize and to evaluate the therapeutic potential of new benzodioxole derivatives (3-14) candidates for schistosomicidal drugs. All compounds synthesized showed in vitro schistosomicidal activity. The derivative 12 was considered the best compound, since it took 100% of worms to mortality in the first 72 h of exposure at the concentration of 100 μM and 83.3% at the concentration of 50 μM. Furthermore, male and female adult worms, incubated for 24 h with the compound 12 showed tegument damages characterized by extensive desquamation and edema, tuber destruction, bubble formation and exposure of the muscle layer. This compound has a restricted structure, where the thiazolidinone is attached to the 4-position of the 1,3-benzodioxol ring. The structural conformation of derivative 12 was probably responsible for the promising schistosomicidal activity, where the presence of an electron/conformational restriction of the thiazolidine ring, as well as the action of bromine as a bulk substitute, favored an increase in biological activity. In addition, tegumentary changes caused by derivative 12 may also have been responsible for the death of adult worms of Schistosoma mansoni. Therefore, we verified that the results obtained in this study make benzodioxole derivatives possible candidates for prototypes of new schistosomicidal drugs.
DeCS
AnimaisSobrevivência Celular / efeitos de drogas
Dioxoles / química
Dioxoles / farmacologia
Dioxoles / uso terapêutico
Células HeLa
Humanos
Microscopia, elétron, varredura
Praziquantel / farmacologia
Praziquantel / uso terapêutico
Schistosoma mansoni / efeitos de drogas
Schistosoma mansoni / ultraestrutura
Esquistossomose / quimioterapia
Esquistossomose / patologia
Esquistossomicidas / síntese química
Esquistossomicidas / farmacologia
Esquistossomicidas / uso terapêutico
Share