Inhibition of Farnesyl Protein Transferase by Ortho-substituted Cinnamaldehyde Derivatives

Various cinnamaldehyde derivatives were synthesized and their inhibition activity $(pI_{50})$ of farnesyl protein transferase (FPTase) was measured to examine the structure-activity relationships (SAR) on the basis that FPTase was inhibited by ortho-hydroxycinnamaldehyde derived from extracts of the bark of Cinnamomum cassia Blume. The ortho-substituents on the phenyl backbone of cinnamaldehyde showed higher activity than those with meta- and para-substituents, and the side chain required unsaturated aldehyde. In particular, 2-chlorocinnamaldehyde, 5 showed the highest inhibition activity on the FPTase among them and its inhibition activity $(pI_{50})$ value was 4.45.