New modulated design and synthesis of chiral CuII/SnIV bimetallic potential anticancer drug entity: In vitro DNA binding and pBR322 DNA cleavage activity

A new chiral ligand scaffold L derived from (R)-2-amino-2-phenyl ethanol and diethyl oxalate was isolated and thoroughly characterized by various spectroscopic methods. The ligand L was allowed to react with CuCl2·2H2O and NiCl2·6H2O to achieve monometallic complexes 1 and 2, respectively. Subsequently modulation of 1 and 2 was carried out in the presence of SnCl4·5H2O to obtain heterobimetallic potential drug candidates 3 and 4 possessing (CuII/SnIV and NiII/SnIV) metallic cores, respectively and characterized by elemental analysis and spectroscopic data including 1H, 13C and 119Sn NMR in case of 3 and 4. In vitro DNA binding studies revealed that complex 3 avidly binds to DNA as quantified by Kb and Ksv values. Complex 3 exhibits a remarkable DNA cleavage activity (concentration dependent) with pBR322 DNA and the cleavage activity of 3 was significantly enhanced in the presence of activators and follows the order H2O2 > Asc > MPA > GSH. Complex 3 cleave pBR322 DNA via hydrolytic pathway and accessible to major groove of DNA.

In vitro DNA binding studies of (R)-enantiomeric form of ligand L, and complexes (1–4) were carried out employing UV–vis titrations, fluorescence and circular dichoric studies to outline the effect of chirality on DNA binding propensity.Figure optionsDownload as PowerPoint slideHighlights
► DNA binding studies revealed that complex 3 binds to DNA via dual mode of binding.
► Cleavage activity of 3 was enhanced in the presence of activators: H2O2 > Asc > MPA > GSH.
► The complex 3 was accessible to major groove as depicted in the cleavage pattern.