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

Abstract

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 10μg/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.