The functional group on (E)-4,4'-disubstituted stilbenes influences toxicity and antioxidative activity in differentiated PC-12 cells.

This work probes the relationship between stilbene functional group and biological activity. The biological activity of synthesized stilbenes (E)-4,4'-dicyanostilbene, (E)-4,4'-diacetylstilbene, (E)-4,4'-diaminostilbene, a novel stilbene, 1,1'-(vinylenedi-p-phenylene)diethanol, and (E)-stilbene was assessed at biologically relevant nanomolar concentrations using the MTS cell viability assay in differentiated PC-12 cells under optimal culture conditions and conditions of oxidative stress. Under optimal culture conditions the synthesized stilbene derivatives were found to be non-toxic to cells at concentrations up to 10 μg/ml. To mimic oxidative stress, the activity of these stilbene derivatives in the presence of 0.03% H2O2 was investigated. Stilbene derivatives with electron-withdrawing functional groups were 2-3 times more toxic than the H2O2 control, indicating that they may form toxic metabolites in the presence of H2O2. Fluorescence data supported that stilbene derivatives with electron-withdrawing functional groups, (E)-4,4'-dicyanostilbene and (E)-4,4'-diacetylstilbene, may react with H2O2. In contrast, the stilbene derivative with a strong electron-donating functional group, (E)-4,4'-diaminostilbene, rescued neurons from H2O2-induced toxicity. The DPPH assay confirmed that (E)-4,4'-diaminostilbene is able to scavenge free radicals. These data indicate that the Hammett value of the functional group correlates with the biological activity of (E)-4,4'-disubstituted stilbenes in differentiated PC-12 cells.