Ecocatalysed Hurtley reaction: Synthesis of urolithin derivatives as new potential RAGE antagonists with anti-ageing properties

Abstract Two ecocatalysts Eco-MG1 and Eco-MG2 were obtained from the biomass of Miscanthus x giganteus cultivated in situ on metal-contaminated soils from the North-of-France region. Ecocatalysts have been characterized by SEM-EDS analyses and flame atomic absorption spectrometry and used to synthesize new urolithins A and B derivatives, metabolites of ellagic acid, through Hurtley reaction between polyphenols and bromobenzoic acids in water and/or in ethanol. Eco-MG2 was the most effective catalyst in the synthesis of urolithin derivatives and exceeded the catalytic power of copper sulphate (CuSO4) conventionally used in this benzo[c]chromene ring-closure Hurtley reaction. Newly synthesized urolithins 1–24 have been evaluated for their ability to inhibit the AGE2-BSA/sRAGE interaction and compared to known RAGE antagonists (Azeliragon, FPS-ZM1, etc). Urolithins showed excellent inhibitory activities equivalent to reference Azeliragon and constitute promising RAGE antagonists with anti-ageing properties. The first SAR were identified and open the way to the development of new series of experimental drugs targeting RAGE.