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 mu M, respectively, as compared against pepstatin (0.0023 mu M), 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. (c) 2006 Elsevier Ltd. All rights reserved.