Planejamento e síntese de novos derivados N-fenilacrilamidas e N-acilidrazônico utilizando ferramentas da Química Medicinal, e suas avaliações como potenciais agentes anti-inflamatórios

Abstract

The search for new effective anti-inflammatory drugs that can be used as an alternative to those already on the market has been motivated by the various side effects caused by the continuous use of these drugs. In this context, the search for new chemical entities with potential anti-inflammatory action has been constant in academics and the pharmaceutical industry, especially those that present good efficacy and selectivity, with low toxicity and low production cost. Among these new chemical entities we highlight the N-acylhydrazonic and N-phenylacetamide derivatives that were chosen for their reports on anti-inflammatory activity. The aim of this study was to synthesize, characterize and evaluate the anti-inflammatory profile in silica of new N-phenylacetamide and N-acylhydrazone derivatives based on structures of promising prototypes JMPR and AMZ-BZ used by our research group. For this, new derivatives were synthesized from prototypes through amidation reactions, followed by condensation using adapted reaction conditions, after evaluating their physical-chemical properties. The structural characterization of the composite compounds: A-07DZ, B-17DZ, C-27DZ and D-37DZ was carried out by spectroscopic techniques of infrared and nuclear magnetic resonance, which allowed the verification of the structural elucidation of the planned compounds. Fragment-based drug design (FBDD) and structure-based drug discovery (SBDD) techniques were used, as well as molecular simplification tools and non-classical bioisosterism. All methodologies are well described in the literature and the synthetic routes already known by our research laboratory. What made possible the synthesis of these new four initiates. The unknown dockings that signalers are promising against the course of the inflammatory process, showing greater secretion with ligands co-crystallized in the enzymes nitric oxide synthase, enzyme dihydroorotate dehydrogenase, enzyme Phosphodiesterase 4B and enzyme Prostaglandin E synthase, when detected with the prototypes. With emphasis on the B-17DZ molecule, which was indicated as a possible promising target for the development of studies involving the evaluation of anti-inflammatory activity (in vitro and in vivo) and in vitro toxicity test, for the continuation of a candidate for drug.