Phenyl carbohydrazone conjugated 2-oxoindoline as a new scaffold that augments the DNA and BSA binding affinity and anti-proliferative activity of a 1,10-phenanthroline based copper(II) complex

•Benzoyl hydrazone conjugated isatin based Cu(II) complex has been synthesized and characterized.•The complex shows efficient DNA and BSA binding propensity.•The complex shows a better cytotoxicity towards cancer cells (HeLa and MCF-7) over noncancer ones (MCF-10a).

A new type of copper(II) complex, [CuL(phen)2](NO3) (CuIP), where L ((E)-N′-(2-oxoindolin-3-ylidene)benzohydrazide) is a N donor ligand and phen is the N, N-donor heterocyclic 1,10-phenanthroline, has been synthesized. The phenyl carbohydrazone conjugated isatin-based ligand L and CuIP were characterized by elemental analysis, infrared, UV–Vis, 1H and 13C NMR and ESI-mass spectral data, as well as single-crystal X-ray diffraction. The interaction of calf thymus DNA (CT DNA) with L and CuIP has been investigated by absorption, fluorescence and viscosity titration methods. The complex CuIP displays better binding affinity than the ligand L. The observed DNA binding constant (Kb = 4.15(±0.18) × 105 M−1) and binding site size (s = 0.19), viscosity data together with molecular docking studies of CuIP suggest groove binding and/or a partial intercalative mode of binding to CT DNA. In addition, CuIP shows good binding propensity to the bovine serum albumin (BSA) protein, giving a KBSA value of 1.25(±0.24) × 106 M−1. In addition, the docking studies on DNA and human serum albumin (HSA) CuIP interactions are consistent with the consequence of binding experiments. The in vitro anti-proliferative study establishes the anticancer potency of the CuIP against the human cervical (HeLa) and breast (MCF7) cancer cells; noncancer breast epithelial (MCF10a) cells have also been investigated. CuIP shows better cytotoxicity and sensitivity towards cancer cells over noncancer ones than L under identical conditions, with the appearance of apoptotic bodies.

Graphical abstractA phenyl carbohydrazone conjugated isatin scaffold bis-1,10-phenanthroline Cu(II) complex has been synthesized and structurally characterized. It displays efficient DNA/BSA binding propensity and significant apoptotic cytotoxicity in HeLa and MCF-7 cancer cells while being non-toxic to MCF-10a normal cells.Figure optionsDownload full-size imageDownload as PowerPoint slide