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-δ-viniferin, deriving from trans-resveratrol dimerization, was investigated in its ability to target DNA duplex G-quadruplex structures by exploiting NMR spectroscopy, circular dichroism, fluorescence spectroscopy molecular docking. (±)-trans-δ-Viniferin proved bind both the minor major grooves of duplexes, whereas it bound 3’- 5’-ends a stacking on outer quartets, accompanied rearrangement flanking residues. Specifically, (±)-trans-δ-viniferin demonstrated higher affinity for targets than monomeric counterpart. Additionally, methoxylated derivatives trans-resveratrol, i. e. (±)-pterostilbene-trans-dihydrodimer trans-pterostilbene, respectively, were evaluated, revealing similar binding modes, affinities stoichiometries as their parent analogues. All tested cytotoxic at μM concentration cell lines, showing damaging activity consistent tightly interact structures.