Preparação de N-sulfonil-1,2,3-triazóis e avaliação do efeito na produção de mediador pró-inflamatório
Data
2023-05-05
Autores
Zandoná, Diego Willian Legori 
Orientadores
Raminelli, Cristiano
Tipo
Dissertação de mestrado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Existem diversos estudos envolvendo compostos 1,2,3-triazólicos 1,4-dissubstituídos, que apresentam atividades biológicas contra bactérias, fungos, tumores e protozoários. Em relação aos processos inflamatórios, existe uma carência de estudos envolvendo triazóis. Assim, através do presente trabalho avaliamos o efeito de compostos N-sulfonil-1,2,3-triazólicos na indução da produção in vitro de óxido nítrico (NO), um mediador próinflamatório. Foram preparados seis N-sulfonil-1,2,3-triazóis (3a-f), por reações de cicloadição entre alcinos terminais e toluenossulfonilazida catalisadas por acetato de cobre (II) e 2aminofenol, em rendimentos na faixa de 67 a 90%. Os compostos 3a-f foram identificados por suas propriedades físicas e tiveram as suas estruturas determinadas por métodos espectroscópicos. Adicionalmente, os compostos N-sulfonil-1,2,3-triazólicos 3a-f apresentaram citotoxicidades não significativas, através de ensaios com brometo de 3-(4,5-dimetil2tiazolil)-2,5-difenil-2-H-tetrazólio (MTT). Em seguida, os compostos 3a-f tiveram os seus efeitos na indução da produção de óxido nítrico (NO) avaliados na linhagem celular macrofágica murina J774. A substância 3c, nas concentrações de 25 μM e 50 μM, apresentou inibições significativas na produção de íons nitrito (gerados por NO), exibindo potencial imunomodulador (antiinflamatório).
There are several studies involving 1,4-disubstituted 1,2,3-triazole compounds, which present biological activities against bacteria, fungi, tumors, and protozoa. In relation to inflammatory processes exist a lack of studies involving triazoles. Therefore, through the present work we evaluated the effect of N-sulfonyl-1,2,3-triazole compounds on the induction of the in vitro production of nitric oxide (NO), a proinflammatory mediator. We prepared six N-sulfonyl-1,2,3-triazoles (3a-f), by cycloaddition reactions between terminal alkynes and ptoluenesulfonyl azide catalyzed by copper (II) acetate and 2-aminophenol, in yields in the range of 67 to 90%. Compounds 3a-f were identified by their physical properties and had their structures determined by spectroscopic methods. In addition, the N-sulfonyl-1,2,3-triazole compounds 3a-f presented nonsignificant cytotoxicities, through assays with 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT). Afterwards, compounds 3a-f had their effects on the induction of the production of nitric oxide (NO) evaluated in murine macrophage cells line J774. The substance 3c, at concentrations of 25 μM and 50 μM, presented significant inhibitions in the production of nitrite ions (generated by NO), exhibiting immunomodulador potential (antiinflammatory).
There are several studies involving 1,4-disubstituted 1,2,3-triazole compounds, which present biological activities against bacteria, fungi, tumors, and protozoa. In relation to inflammatory processes exist a lack of studies involving triazoles. Therefore, through the present work we evaluated the effect of N-sulfonyl-1,2,3-triazole compounds on the induction of the in vitro production of nitric oxide (NO), a proinflammatory mediator. We prepared six N-sulfonyl-1,2,3-triazoles (3a-f), by cycloaddition reactions between terminal alkynes and ptoluenesulfonyl azide catalyzed by copper (II) acetate and 2-aminophenol, in yields in the range of 67 to 90%. Compounds 3a-f were identified by their physical properties and had their structures determined by spectroscopic methods. In addition, the N-sulfonyl-1,2,3-triazole compounds 3a-f presented nonsignificant cytotoxicities, through assays with 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT). Afterwards, compounds 3a-f had their effects on the induction of the production of nitric oxide (NO) evaluated in murine macrophage cells line J774. The substance 3c, at concentrations of 25 μM and 50 μM, presented significant inhibitions in the production of nitrite ions (generated by NO), exhibiting immunomodulador potential (antiinflammatory).