Zinc(II) complexes of indole thiosemicarbazones: DNA/protein binding, molecular docking and in vitro cytotoxicity studies

Abstract

Four Zn(II) complexes (1–4) featuring indole thiosemicarbazones were synthesized and well-characterized by elemental analyses and various spectroscopic (UV–Vis, FT-IR, 1H NMR, 13C NMR and mass) techniques. The single crystal X-ray crystallographic study revealed a tetrahedral geometry for complexes 1 and 3. The interactions of the Zn(II) complexes 1–4 with calf thymus DNA (CT DNA) were examined by UV–Vis spectroscopy and viscosity measurements, which implied that the complexes bound to CT DNA via intercalation, and complex 4 showed a higher binding affinity than the other complexes. The protein binding interaction of the complexes was monitored by fluorescence and absorption techniques, which showed that the complexes could bind effectively with bovine serum albumin (BSA) and the type of quenching mechanism was found to be static. Synchronous fluorescence experiments showed the changes in the conformations of the protein micro regions. Molecular docking studies were performed in order to get a better picture of the binding of the complexes with the molecular targets DNA hexamer and BSA. The in vitro cytotoxicity of the complexes against two human cancer (A549 and MCF7) cell lines, two human non-tumorigenic (MCF-10A and HEK-293) cell lines and one non-cancerous mouse fibroblasts (L929) cell line was evaluated using an MTT assay. Complex 4, which has an N-terminal cyclohexyl group, showed moderate activity [IC50 = 37.9 (A549) and 60.3 μM (MCF7)] that was comparable with the familiar anticancer drug cisplatin. Also, fortunately, the activity of complex 4 was found to be specific to cancer cells. The apoptosis cell death mechanism for complex 4 was assessed by the Hoechst staining method.