Síntese e estudo in silico de derivados de naproxeno com potencial atividade anti-inflamatória

Abstract

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the drugs most commonly used among therapeutic agents. However results of clinical studies indicate that adverse effects caused by these drugs include increased risk of gastrointestinal bleeding, dyspepsia, peptic ulcer disease, and renal failure, platelet aggregation inhibition and increase of bleeding time, changes in renal function tests among others. Thus the present work seeks to contribute to research aimed at minimizing the adverse effects caused by NSAIDs. For this held synthesis of derivatives of naproxen esters and evaluated in silico anti-inflmatória potential activity of these compounds. four compounds were synthesized: the naproxenato of Timila, carvacrila, eugenila and vanilinila. In silico study in the ADMET properties were evaluated to examine the bioavailability of the drug candidate compounds, as well as the study of molecular docking with the COX-1 and COX-2 enzymes. By evaluating the admetSar tool, Osiris and Molinspiration is possible to supplement the compounds evaluated derivatives exhibit good oral availability, have no toxicity compared to precursor tap, they are not carcinogenic, but a disadvantage is that some of the compounds show higher promiscuity in relation to inhibition of some enzymes of the cytochrome P 450, which may result in lower efficiency of fármaco.No molecular docking study demonstrated that the compounds exhibit higher interaction energy values with the COX-2 enzyme than the COX-1 enzyme. The evaluated compounds interact with both isoforms of COX, but exhibit favorable interactions both in energy and in location to the COX-2 enzyme. The synthesis of naproxen derivatives was performed and the naproxenato compounds Timila and eugenila synthesized were characterized by 1H and 13C NMR chemical debonding having consistent with literature data.