Plant-Derived Stilbenoids as DNA-Binding Agents: From Monomers to Dimers

Stilbenoids are natural compounds endowed with several biological activities, including cardioprotection and cancer prevention. Among them, (+/-)-trans-delta-viniferin, deriving from trans-resveratrol dimerization, was investigated in its ability to target DNA duplex and G-quadruplex structures by exploiting NMR spectroscopy, circular dichroism, fluorescence spectroscopy and molecular docking. (+/-)-trans-delta-Viniferin proved to bind both the minor and major grooves of duplexes, whereas it bound the 3'- and 5'-ends of a G-quadruplex by stacking on the outer quartets, accompanied by rearrangement of flanking residues. Specifically, (+/-)-trans-delta-viniferin demonstrated higher affinity for the investigated DNA targets than its monomeric counterpart. Additionally, the methoxylated derivatives of (+/-)-trans-delta-viniferin and trans-resveratrol, i. e. (+/-)-pterostilbene-trans-dihydrodimer and trans-pterostilbene, respectively, were evaluated, revealing similar binding modes, affinities and stoichiometries with the DNA targets as their parent analogues. All tested compounds were cytotoxic at mu M concentration on several cancer cell lines, showing DNA damaging activity consistent with their ability to tightly interact with duplex and G-quadruplex structures.

Automated summary

The natural compound stilbenoids, including (+/-)-trans-delta-viniferin, have shown the ability to bind to both DNA duplex and G-quadruplex structures, with higher affinity for the DNA targets compared to their monomeric counterparts. These compounds exhibit cytotoxicity and DNA damaging activity on cancer cell lines.