Novas Tiazolidinadionas 3, 5-Dissubstituidas: sÃntese, comprovaÃÃo estrutural e avaliaÃÃo da atividade antiinflamatÃria

AUTOR(ES)
DATA DE PUBLICAÇÃO

2008

RESUMO

To the thiazolidinic nucleus, due to their chemical reactivity, are atributed several biological activities, fact that directed our research in search of new biologically active agents. Recent studies have demonstrated the potential of thiazolidinics derivatives in inhibiting the inflammatory response, characterized by the release of various endogenous pro-inflammatory mediators (prostaglandins and leukotrienes) from the conversion of arachidonic acid by the cyclooxygenase and lipoxygenase enzymes. Some studies have linked this activity to the activation of PPARγ receptor, because of thiazolidinas are synthetic ligands of these receptors. In this work three compounds were synthesized in the series 5-benzylidene-3-(4-methyl-benzyl)-thiazolidine-2,4-dione (LPSF/GQ-14, LPSF/GQ-18, LPSF/GQ-21) and four compounds of the series 5-benzylidene-3-(2,4-dichloro-benzyl)-thiazolidine-2,4-dione (LPSF/GQ-108, LPSF/GQ- 109, LPSF/GQ-235, LPSF/GQ-265). The preparation of these thiazolidinics derivatives was conducted from the reaction of addition of Michael between 3-(4-methyl-benzyl)-thiazolidine-2,4-dione (LPSF/GQ-1) and 3-(2.4-dichloro-benzyl)-thiazolidine-2,4-dione (LPSF/GQ-53) with substituted derivatives ethyl-(2-cyano-3-phenyl)-acrylates (LPSF/IP). These derivatives were obtained in a satisfactory manner with yield in last stage between 35 and 83%. The chemical structures were properly supported by nuclear magnetic resonance hydrogen (RMN1H), and infrared. Six compounds (LPSF/GQ-14, LPSF/GQ-18, LPSF/GQ-108, LPSF/GQ-109, LPSF/GQ-235 e LPSF/GQ-265) were choosed and their antiinflammatory activity was evaluated in the inflammation model of peritonitis carrageenan-induced in mice. All tested representatives of the series mentioned above showed significant antiinflammatory activity with percentage of inhibition of cell migration varying between 43 and 79%. The compound LPSF/GQ-235 proved to be the most active among the compounds tested in the dose of 3 mg/Kg, reaching a level of inhibition of 79% of cell migration and 97% of Rosiglitazoneâs activity (reference compound). The results are important and show the potential of thiazolidinics derivatives replaced in positions 3 and 5 as candidates for new antiinflammatory agents

ASSUNTO(S)

ciencias biologicas thiazolidinone antiinnflamatory tiazolidinona atividade antiinflamatÃria

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