SÃntese, comprovaÃÃo estrutural, modelagem molecular e avaliaÃÃo da atividade antiinflamatÃria de novos derivados tiazolidÃnicos

AUTOR(ES)

Cleiton Diniz Barros

DATA DE PUBLICAÇÃO

2008

RESUMO

Among the pathology that the involved inflammatory process deserves the outstanding rheumatoid arthritis, cancer and acute pancreatitis, where the latter can be originated by a chronic inflammation. Some inflammatory mediators are observed from these diseases, such as TNF-α, iNOS, and NF-kB that are properly modulated by PPARs (Peroxisome proliferator-activated receptors). The need for new antiiflammatory drugs with lower adverse effects directed researchers to intensify the research for the discovery of new compounds. The datas found in the literature demostrated the TZDs as synthetics ligands of PPARs and therefore, they have inhibitory activity of inflammation. With this purpose, giving continuity to the work accomplished in the laboratory of Synthesis and Planning Drugs (LPSF / GPIT / UFPE), we synthesized new compound arylidene-thiazolidine-2,4-diones (ATZDs) of the series: 5-benzylidene-3-(2-bromo-benzyl)-thiazolidine-2,4-dione (LPSF/QG), 5-benzylidene-3-(3-chloro-benzyl)-thiazolidine-2,4-dione (LPSF / TA). Based on TZD, the derivatives synthetized were obtained by N-alkylation reactions in position 3 of TZD, and by Michael addition reaction in the position 5. The chemical structures of the synthesized compounds were properly confirmed by the nuclear magnetic resonance spectroscopy of hydrogen (NMR 1H), infrared and mass spectrometry. Also, the antiinflamatory activities were evaluated by the experimental method in vivo, air pouch induced by carrageenan, at doses of 0.03, 0.3 and 3 mg / kg. The conformational structure of the representatives of the series LPSF / TA and LPSF / GQ, was via "docking", and their interaction was observed in the Peroxisome proliferator-activated receptors of the gama type (PPAR γ). We observed that the derivatives 3-(2-bromo-benzyl)-5-(4-methylsulfonyl-benzylidene)-thiazolidine-2,4-dione (LPSF/GQ-58), 3-(3-chloro-benzyl)-5-(4-methylsulfonyl-benzylidene)-thiazolidine-2,4-dione (LPSF/TA-02) and 5-Bipheny-4-ylmethylene-3-(3-chloro-benzyl)-thiazolidine-2,4-dione (LPSF/TA-03) that presenting the best antiinflamatory activity, present too the best docking results in the PPARγ

ASSUNTO(S)

sÃntese orgÃnica antiinflamatÃrio farmacia antiinflamatory organic synthesis tiazolidinas tzds

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