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

- Enantiomeric Cu(II)/Ni(II) complexes were synthesized from a reduced Schiff base.
- l-Enantiomeric Cu(II) complex 1a revealed high DNA binding affinity.
- Complex 1a showed efficient DNA cleavage via oxidative pathway mechanism.
- Complex 1a divulged potential cytotoxicity towards specific cancer cell lines.
- Molecular modeling studies correlated with the in vitro DNA binding results.

New chiral reduced Schiff base ligands, L1 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(II) 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 Kb, K and Ksv values of 1 & 2 (a and b) which demonstrated higher binding affinity of l-enantiomeric Cu(II) complex, 1a and followed the order as 1a > 1b > 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 1a 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 (1O2) and the superoxide anion (O2
- -) 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 1a demonstrated binding affinity towards DNA ascertained from its higher binding energy values. Furthermore, the cytotoxic assessment of 1a 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.

Graphical AbstractDNA groove binding and condensation reactions of l-enantiomeric Cu(II) complex (1a).