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 center dot 2H(2)O and NiCl2 center dot 6H(2)O to achieve monometallic complexes 1 and 2, respectively. Subsequently modulation of 1 and 2 was carried out in the presence of SnCl4 center dot 5H(2)O 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 H-1, C-13 and Sn-119 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 H2O2 > Asc > MPA > GSH. Complex 3 cleave pBR322 DNA via hydrolytic pathway and accessible to major groove of DNA. (C) 2012 Elsevier B.V. All rights reserved.