Discovery of Fuchsone Derivatives as Novel Nonpeptide Inhibitor of Caspase-3

Many degenerative diseases caused by uncontrolled cell death can be intervened pharmaceutically through inhibiting caspase-3 activity that leads to cell apoptosis. Here is presented the discovery of rosolic acid and phenolphthalein methyl ester, which both belong to fuchsone derivatives, as novel and potent nonpeptide inhibitors of caspase-3. They show high inhibitory potency against caspase-3 in vitro(IC₅₀=0.28 and 0.13 μmol/L). Molecular modeling study provided further an insight into the interaction of phenolphthalein methyl ester with activated caspase-3. The structures of the present small-molecule caspase-3 inhibitors are different from the structures of known caspase-3 inhibitors, so the inhibitors were likely to provide some information for the discovery of anti-caspase-3 inhibitors.