Synthesis and characterization of potential pro-resolving inflammation compounds

Promotion of resolution of inflammation has been studied as a novel strategy for the treatment of chronic inflammatory diseases. Specialized pro-resolving lipid mediators such as Resolvin E1 – eicosapentaenoic omega-3 fatty acid metabolite – are powerful inducers of resolution, however, even though some authors consider them as drug candidates, they have unfavorable structural characteristics. A series of nine com-pounds and one intermediate was synthesized, using the structures of Resolvin E1 and its analog RX10008, which reached Phase II clinical studies, as a model of chemical similarity. Two compounds of them were considered to be the most promising, considering both 3D-similarities with minimum energy conformers of Resolvin E1 and RX10008, calculated with vROCs software. These compounds synthesized were evaluated in terms of cell viability and TNF-alpha inhibition by the MTT and ELISA assay, all were non-cytotoxic and showed inhibitory TNF-alpha activity, at the concentrations tested (25, 50 and 100 μM).