Resveratrol is a natural polyphenol which has been studied for its potential benefits for several pathological processes including cancer, aging, CVS disorders, chronic inflammation, and neurodegenerative diseases. Nevertheless, its poor ADME profile limits its application. Aiming to improve its pharmacokinetic properties and anti-inflammatory activity, we designed, prepared and evaluated some methylated resveratrol-NSAID hybrids connected through an amide bond. These compounds were prepared from 4-vinylaniline using a palladium-catalyzed oxidative-Heck coupling as the key step in moderate yields. Docking studies predicted that they could bind to both COX-1 and COX-2 with the NSAID template interacting via hydrogen bonds with Arg 120 and Tyr 355 and the dimethoxystilbene moiety accommodates closer to the heme group. All compounds had from moderate to good in vitro antioxidant properties, though lower than resveratrol. Compound 1c had the best anti-inflammatory properties in the TPA-induced edema test and could be considered a good starting point for the design of novel hybrids with better antioxidant and anti-inflammatory properties.

Design, synthesis, and evaluation of resveratrol-NSAID hybrids as potential antioxidants and anti-inflamatories

2019 Spring National Meeting

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