Synthesis of gallic acid based naphthophenone fatty acid amides as cathepsin D inhibitors

Gallic acid, one of the most abundant plant phenolic acids, has been modified to cathepsin D protease inhibitors. The strategy of modification was proposed basing on some previously reported structure and activity relationship (SAR) studies. The synthesized naphthophenone fatty acid amide derivatives have been evaluated for in vitro cathepsin D inhibition activity. Two of them have shown significant inhibition activity with IC50 values of 0.06 and 0.14 μM, respectively, as compared against pepstatin (0.0023 μM), the most potent inhibitor known so far. The study revealed that such attempts on gallic acid based pharmacophores might result in potent inhibitors of cathepsin D.

Gallic acid has been modified to naphthophenone fatty acid amide derivatives. The targeted amides had a conformationally restricted pharmacophore and a linear aliphatic chain based on structure and activity relationship of previous studies. Two of the derivatives have shown significant cathepsin D inhibition activity having IC50 values 0.056 and 0.136 μM.Figure optionsDownload as PowerPoint slide