9Th Brazilian Symposium on Medicinal Chemistry

This project aims the synthesis and study of amides derived from nonsteroidal anti-inflammatory drugs (NSAIDs) and their derived S-Nitrosothiols. These compounds are potential prodrugs with less side effects, and appropriate selectivity to the different cyclooxygenase isoforms. The anti-inflammatory activity of those compounds has being evaluated in vitro through reduction of IL (interleukine)-12 levels produced by macrophages previously activated with interferon-gamma and lipopolysaccharide. Amides were prepared reacting the NSAIDs with heterocyclic aromatic amines and with L-cysteine ethyl ester hydrochloride by coupling reactions with carbodiimiides and CDI, in: ethanol, dichlorometane, and dimethyl carbonate (defined as a green condition). In silico analysis are being carried out for this molecules. Results obtained for the in vitro assays for anti-inflammatory activity are showing positive results. The use of environmentally friendly methodologies for the coupling reactions is providing very promising results. These methodologies are becoming a relevant alternative for the preparation of the compounds of interest.