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

Abstract

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(2)O and NiCl(2)·6H(2)O to achieve monometallic complexes 1 and 2, respectively. Subsequently modulation of 1 and 2 was carried out in the presence of SnCl(4)·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 (1)H, (13)C and (119)Sn 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(2)O(2)>Asc>MPA>GSH. Complex 3 cleave pBR322 DNA via hydrolytic pathway and accessible to major groove of DNA.