In vitro DNA binding profile of enantiomeric dinuclear Cu(II)/Ni(II) complexes derived from L-/D-histidine-terepthaldehyde reduced Schiff base as potential chemotherapeutic agents

New chiral reduced Schiff base ligands, Ll and L2 derived from L-/D-histidine and terepthaldehyde, and their Cu(II) and Ni(II) dinuclear complexes 1 & 2 (a and b) were synthesized and thoroughly characterized by various spectroscopic techniques. Comparative binding profile of both L-/D-enantiomeric Cu(I1) and Ni(II) complexes with ct-DNA was studied by employing optical and spectroscopic techniques to evaluate their enantiopreferential selectivity towards molecular target DNA and thereby explore their relative chemotherapeutic potential. Quantitative assessment of DNA binding propensity was ascertained by calculating K-b, K and K-sv values of 1 & 2 (a and b) which demonstrated higher binding affinity of L-enantiomeric Cu(II) complex, la and followed the order as la > lb > 2a > 2b. Scanning electron microscopy (SEM) was used to analyze the morphological changes of the DNA condensate in presence of complexes 1 (a and b). The SEM micrographs condensates revealed morphological transitions and formation of different structural features implicating the condensation process between the complexes and biomolecule occurred to form compact massive structures. The gel electrophoretic assay of complex la was carried out with pBR322 plasmid DNA which revealed an efficient cleaving ability of the complex via oxidative pathway with the involvement of singlet oxygen (102) and the superoxide anion (O-2(center dot-)) radicals as the ROS responsible the cleavage reactions. Molecular docking studies of 1 (a and b) with DNA revealed selective recognition of G-C residues of the narrow minor groove of the DNA duplex and complex la demonstrated binding affinity towards DNA ascertained from its higher binding energy values. Furthermore, the cytotoxic assessment of la was examined on a panel of cancer cell lines of different histological origin employing SRB assay which revealed remarkably good cytotoxic activity towards HL60, HeLa and MCF7 cancer cell lines. (C) 2016 Elsevier B.V. All rights reserved.