New modulated design and synthesis of chiral Cu II/Sn IV bimetallic potential anticancer drug entity: In vitro DNA binding and pBR322 DNA cleavage activity

作者：Tabassum S^*; Sharma G C; Arjmand F

来源：Spectrochimica Acta - Part A: Molecular and Biomolecular Spectroscopy , 2012, 90: 208-217.

DOI：10.1016/j.saa.2012.01.020

• 5&prime
• -GMP
• CT DNA
• Groove binding
• Hydrolytic cleavage
• Nuclease activity
• pBR322 DNA

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 CuCl 2·2H 2O and NiCl 2·6H 2O to achieve monometallic complexes 1 and 2, respectively. Subsequently modulation of 1 and 2 was carried out in the presence of SnCl 4·5H 2O to obtain heterobimetallic potential drug candidates 3 and 4 possessing (Cu II/Sn IV and Ni II/Sn IV) 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 K b and K sv 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 H 2O 2 Asc MPA GSH. Complex 3 cleave pBR322 DNA via hydrolytic pathway and accessible to major groove of DNA.