Síntese de novos derivados de éteres de oximas e avaliação farmacológica de suas propriedades anti-inflamatórias

Abstract

The inflammatory process consists is a biological response in a living organism against some kind of physical, biological or chemical attack. The inflammatory response is mediated by substances called chemical mediators. One of the mediators is arachidonic acid and its metabolites are responsible for the inflammatory process. The arachidonic acid cascade produces the main inflammatory mediators such as leukotrienes, prostaglandins and thromboxanes. Non-steroidal anti-inflammatory drugs act by inhibiting prostaglandin endoperoxide synthase or cyclooxygenase enzymes that are responsible for oxidation of arachidonic acid and which have two isoforms: a PGHS-1, also known as cyclooxygenase 1 (COX-1) which is a constitutive enzyme because of its presence in physiological processes and PGHS-2, also known as cyclooxygenase 2 (COX-2) which can be induced by the inflammatory process. Anti-inflammatory drugs highly selective for PGHS 2 have been developed. However, some of them showed adverse effects and were withdrawn from the market, the following being examples: lumiracoxib (Prexige ®), etoricoxib (Arcoxia ®), parecoxib (Bextra ®), as it was thought that their safety profiles, including serious adverse cardiac, hepatic and renal disease, outweighed the risk-benefit in their intended applications. New prototype of less selective anti-inflammatory drugs have been developed. Compounds containing the functional group oxime ether were synthesized in our research group and their profiles of anti-inflammatory activity were evaluated, and positive results were present leading to continuation of these studies in order to confirm and complement the anti-inflammatory activities already identified. Once synthesized and identified the oxime ethers were subjected to further tests in vivo confirming their anti-inflammatory and analgesic activities, and inhibiting actions on platelet aggregation have also been identified. The tests corroborated to confirm the effectiveness of the pharmacological compounds synthesized by our study group. In this work the synthesis of new derivatives of oxime ethers was also carried out, which were subjective to analysis by RMN 1H and RMN 13C, confirming their structures and their synthetic route.