Synthesis and crystal structure determination of copper(II)-complex: In vitro DNA and HSA binding, pBR322 plasmid cleavage, cell imaging and cytotoxic studies

•New anticancer chemotherapeutic agent was synthesized, characterized by X-ray crystallography.•Complex 1 recognizes minor groove of DNA and inhibited Topo-I activity at a remarkable IC50 ∼20 μM.•Time dependent HPLC revealed; bonded drug with protein releases slowly towards DNA.•Complex 1 exhibited good cytotoxicity against human cancer cell lines.•Live HeLa cell imaging studies of 1 showed its nuclear specific localization.

New Cu(II) complex 1 of indole-3-propionic acid and 1,10-phenanthroline was synthesized and characterized by analytical, spectroscopic and single crystal X-ray diffraction. In vitro DNA binding studies of 1 was performed by employing UV–vis and fluorescence spectroscopic techniques. The binding affinity towards human serum albumin (HSA) was also investigated to understand the carrier role in body system, as the time dependent HPLC experiment of 1 revealed that bonded drug with protein releases slowly in presence of DNA. Complex 1 exhibited good anti-tumor activity (GI50 values <10 μg/ml), and to elucidate the mechanism of tumor inhibition, topoisomerase I enzymatic activity was carried out and further validated by cell imaging studies which clearly showed its nuclear localization.

Graphical abstractNew Cu(II) complex (1) of indole-3-propionic acid and 1,10-phenanthroline was synthesized as potential cancer chemotherapeutic agent targeting DNA using carrier protein HSA.Figure optionsDownload full-size imageDownload as PowerPoint slide