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Synthesis, cytotoxicity and antifungal activity of 5-nitro-thiophene-thiosemicarbazones derivatives.
de Araújo Neto, Luiz Nascimento; do Carmo Alves de Lima, Maria; de Oliveira, Jamerson Ferreira; de Souza, Edson Rubhens; Buonafina, Maria Daniela Silva; Vitor Anjos, Mayara Nunes; Brayner, Fábio André; Alves, Luiz Carlos; Neves, Rejane Pereira; Mendonça-Junior, Francisco Jaime Bezerra.
Afiliação
  • de Araújo Neto LN; Chemistry Laboratory and Therapeutic Innovation, Federal University of Pernambuco, 50670-901, Brazil.
  • do Carmo Alves de Lima M; Chemistry Laboratory and Therapeutic Innovation, Federal University of Pernambuco, 50670-901, Brazil. Electronic address: nenalima.mariadocarmo@gmail.com.
  • de Oliveira JF; Chemistry Laboratory and Therapeutic Innovation, Federal University of Pernambuco, 50670-901, Brazil.
  • de Souza ER; Chemistry Laboratory and Therapeutic Innovation, Federal University of Pernambuco, 50670-901, Brazil.
  • Buonafina MDS; Medical Mycology Laboratory, Federal University of Pernambuco, 50670-901, Brazil.
  • Vitor Anjos MN; Laboratory of Natural Products, Federal University of Pernambuco, 50670-901, Brazil.
  • Brayner FA; Aggeu Magalhães Research Center (FIOCRUZ) and Keizo Asami Immunopathology Laboratory (LIKA), Federal University of Pernambuco, 50740-465, Brazil.
  • Alves LC; Institute of Biological Sciences (ICB), University of Pernambuco, 50100-130, Brazil.
  • Neves RP; Medical Mycology Laboratory, Federal University of Pernambuco, 50670-901, Brazil.
  • Mendonça-Junior FJB; Laboratory of Synthesis and Drug Delivery, State University of Paraiba, 58071-160, Brazil.
Chem Biol Interact ; 272: 172-181, 2017 Jun 25.
Article em En | MEDLINE | ID: mdl-28479098
In the present work, twelve N-substituted 2-(5-nitro-thiophene)-thiosemicarbazones derivatives (L1-12) were synthesized, characterized and their in vitro cytotoxic and antifungal activities were evaluated against Candida sp. and Cryptococcus neoformans. The probable mechanisms of action have been investigated by sorbitol and ergosterol assays. Additionally, ultrastructural study by Scanning Electron Microscopy was performed with the L10 compound. All compounds were obtained in good yield and their chemical structures were characterized on basis of their physico-chemical and Nuclear Magnetic Resonance - NMR, Spectrophotometric Absorption in the Infrared - IR and High-resolution Mass Spectrometry - HRMS data. The results showed that all strains were more sensitive to the compound L10 except Candida tropicalis URM 6551. On the other hand, the cytotoxicity assay by incorporation of tritiated thymidine showed moderate cytotoxic activity on L8 of the 50 µg/mLat which had the best MIC-cytotoxicity relationship. Concerning the study of the possible mechanism of action, the compounds were not able to bind to ergosterol in the membrane, do not act by inhibiting the synthesis of fungal cell wall (sorbitol assay). However, the Scanning Electron Microscopy - SEM analysis shows significant morphological changes in shape, size, number of cells and hyphae, and cell wall indicating a possible mechanism of action by inhibition of enzymes related to the ergosterol biosynthesis pathway. Our results demonstrate that N-substituted 2-(5-nitro-thiophene)-thiosemicarbazones derivatives are potential antifungal agents with activity associated with inhibition of enzymes related to biosynthesis of ergosterol.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Tiossemicarbazonas / Antifúngicos Limite: Animals Idioma: En Revista: Chem Biol Interact Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Brasil País de publicação: Irlanda
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Tiossemicarbazonas / Antifúngicos Limite: Animals Idioma: En Revista: Chem Biol Interact Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Brasil País de publicação: Irlanda