Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/37515
Title: Novel indol-3-yl-thiosemicarbazone derivatives: Obtaining, evaluation of in vitro leishmanicidal activity and ultrastructural studies
Authors: Silva, Paula Roberta da
Oliveira, Jamerson Ferreira de
Silva, Anekécia Lauro da
Queiroz, Camila Marques
Feitosa, Ana Paula Sampaio
Duarte, Denise Maria Figueiredo Araújo
Silva, Aline Caroline da
Castro, Maria Carolina Accioly Brelaz de
Pereira, Valéria Rêgo Alves
Silva, Rosali Maria Ferreira da
Alves, Luiz Carlos
Santos, Fábio André Brayner dos
Lima, Maria do Carmo Alves de
Affilliation: Universidade Federal de Pernambuco. Departamento de Antibióticos. Recife, PE, Brasil.
Universidade Federal de Pernambuco. Departamento de Antibióticos. Recife, PE, Brasil.
Universidade Federal do Vale do São Francisco. Departamento de Medicina. Paulo Afonso, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Departamento de Parasitologia. Recife, PE, Brasil.
Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Departamento de Parasitologia. Recife, PE, Brasil.
Universidade Federal de Pernambuco. Departamento de Antibióticos. Recife, PE, Brasil.
Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Departamento de Imunologia. Recife, PE, Brasil.
Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Departamento de Imunologia. Recife, PE, Brasil / Universidade Federal de Pernambuco. Núcleo de Enfermagem. Vitória de Santo Antão, PE, Brasil.
Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Departamento de Imunologia. Recife, PE, Brasil.
Universidade Federal de Pernambuco. Departamento de Ciências Farmacêuticas. Recife, PE, Brasil.
Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Departamento de Parasitologia. Recife, PE, Brasil.
Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Departamento de Parasitologia. Recife, PE, Brasil.
Universidade Federal de Pernambuco. Departamento de Antibióticos. Recife, PE, Brasil.
Abstract: Parasitic diseases still represent serious public health problems, since the high and steady emergence of resistant strains is evident. Because parasitic infections are distributed predominantly in developing countries, less toxic, more efficient, safer and more accessible drugs have become desirable in the treatment of the infected population. This is the case of leishmaniasis, an infectious disease caused by a protozoan of the genus Leishmania sp., responsible for triggering pathological processes from the simplest to the most severe forms leading to high rates of morbidity and mortality throughout the world. In the search for new leishmanicidal drugs, the thiosemicarbazones and the indole fragments have been identified as promising structures for leishmanicidal activity. The present study proposes the synthesis and structural characterization of new indole-thiosemicarbazone derivatives (2a-j), in addition to performing in vitro evaluations through cytotoxicity assays using macrophages (J774) activity against forms of Leishmania infantum and Leishmania amazonensis promastigote as well as ultrastructural analyzes in promastigotes of L. infantum. Results show that the indole-thiosemicarbazone derivatives were obtained with yield values varying from 32.09 to 94.64%. In the evaluation of cytotoxicity, the indole-thiosemicarbazone compounds presented CC50 values between 53.23 and 357.97 μM. Concerning the evaluation against L. amazonensis promastigote forms, IC50 values ranged between 12.31 and  > 481.52 μM, while the activity against L. infantum promastigotes obtained IC50 values between 4.36 and 23.35 μM. The compounds 2d and 2i tested against L. infantum were the most promising in the series, as they showed the lowest IC50 values: 5.60 and 4.36 respectively. The parasites treated with the compounds 2d and 2i showed several structural alterations, such as shrinkage of the cell body, shortening and loss of the flagellum, intense mitochondrial swelling and vacuolization of the cytoplasm leading the parasite to cellular unviability. Therefore, the indole-thiosemicarbazone compounds are promising because they yield considerable synthesis, have low cytotoxicity to mammalian cells and act as leishmanicidal agents.
Keywords: Indole derivatives
Leishmania amazonensis
Leishmania infantum
Thiosemicarbazone
Ultrastructural studies
DeCS: Indóis / análogos & derivados
Leishmania
Leishmania infantum
Tiossemicarbazonas
Issue Date: 2019
Citation: SILVA, Paula Roberta da et al. Novel indol-3-yl-thiosemicarbazone derivatives: Obtaining, evaluation of in vitro leishmanicidal activity and ultrastructural studies. Chemico-Biological Interactions, p. 1-44, Nov. 2019.
DOI: 10.1016/j.cbi.2019.108899
ISSN: 0009-2797
Copyright: restricted access
Appears in Collections:PE - IAM - Preprint




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