Development, evaluation and effect of anionic co-ligand on the biological activity of benzothiazole derived copper(II) complexes

Research on development of novel metal based anti-cancer agents continues with its popularity among bioinorganic community. Benzothiazole, an important heterocyclic pharmacophore, was chosen as a valuable and useful scaffold for the synthesis of novel copper(II) complexes. Three new copper(II) complexes obtained from the synthesis of newly synthesized benzothiazole based N-(benzo[d]thiazol-2-ylmethyl)-N-methyl-2-(pyridin-2-yl)ethan-1-amine (btzpy) ligand with CuCl2 [Cu(btzpy)Cl2] (1), Cu(NCS)2 [Cu(btzpy)(NCS)2] (2), and Cu(NO3)2 [Cu(btzpy)(NO3)(H2O)]NO3 (3) were isolated and characterized by physical and spectroscopic measurements, including single-crystal X-ray structures. The interaction of complexes 1 and 3 with calf thymus (CT)-DNA was investigated using ethidium bromide fluorescence quenching assay and weak intercalation with KSV values of 9.8 × 102 M−1 and 8.2 × 102 M−1, respectively was observed. All three complexes have shown DNA cleavage of supercoiled plasmid DNA forming single nicked and double nicked forms in the presence of external reducing agents like 3-mercaptopropionic acid (3-MPA) and ascorbic acid. The water-soluble complexes 1 and 3 also show prominent hydrolytic DNA cleavage. From the DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging assay, it was observed that complex 2 also exhibits good antioxidant properties. The cytotoxicity of complexes 1–3 was tested against the lung cancer cell line (A549) and complex 2 with -NCS moiety shows maximum activity in the micromolar range. A rationale for the observed activity is proposed in light of the other properties of these molecules. A novel benzothiazole derived tridentate ligand is utilized for the synthesis of copper(II) complexes with a motive to develop new Cu complexes for therapeutic purposes. Studies on DNA binding, protein binding, nuclease activity, antioxidant activity, and cytotoxicity on lung cancer (A549) cell line are described. [Display omitted] •Development of benzothiazole based Cu(II) complexes for therapeutic purposes•Detailed characterization by various methods including single-crystal X-ray diffraction•DNA binding and nuclease activity showing hydrolytic and oxidative cleavage of DNA•Bovine Serum Albumin (BSA) binding and antioxidant properties have been evaluated•Cytotoxicity study on lung cancer (A549) cell line showing antiproliferative activity