DNA binding, cytotoxicity, apoptotic inducing activity, and molecular modeling study of quercetin zinc(II) complex.

DNA cleavage activity of quercetin zinc(II) complex has been studied, but little attention has been devoted to the relationship between antitumor activity of this complex and DNA-binding properties. DNA-binding properties of quercetin zinc(II) complex were studied using UV-vis spectra, fluorescence measurements, and viscosity measurements. The results obtained indicate that quercetin zinc(II) complex can intercalate into the stacked base pairs of DNA, and compete with the strong intercalator ethidium bromide for the intercalative binding sites with Stern-Volmer quenching constant, K(sq)=1.24. The complex was subjected to biological tests in vitro using three tumor cell lines (HepG2, SMMC7721, and A549), which showed significant cytotoxicity against three tumor cell lines. Moreover, Hoechst33258 staining showed HepG2 cells underwent the typical morphologic changes of apoptosis characterized by nuclear shrinkage, chromatin condensation, or fragmentation after exposure to the complex. In addition, Molecular modeling was performed to learn the complex could be preferentially bound to DNA in GC region. Our results suggest that antitumor activity of quercetin zinc(II) complex might be related to its intercalation into DNA.