Exploring a new family of designer copper(II) complexes of anthracene-appended polyfunctional organic assembly displaying potential anticancer activity via cytochrome c mediated mitochondrial apoptotic pathway

Abstract

The present article describes the systematic study on design and synthesis, physicochemical properties and spectroscopic features, and potential anticancer activities of a family of novel copper(II)-based designer metal complexes [Cu2(acdp)(μ-Cl)(H2O)2] (1), [Cu2(acdp)(μ-NO3)(H2O)2] (2) and [Cu2(acdp)(μ-O2CCF3)(H2O)2] (3) of anthracene-appended polyfunctional organic assembly, H3acdp (H3acdp = N,N′-bis[anthracene-2-ylmethyl]-N,N′-bis[carboxymethyl]-1,3-diaminopropan-2-ol). Synthesis of 1–3 was accomplished under facile experimental conditions, preserving their overall integrity in solution. The incorporation of polycyclic anthracene skeleton within the backbone of organic assembly increases lipophilicity of resulting complexes, thereby dictating the degree of cellular uptake with improved biological activity. Complexes 1–3 were characterized by elemental analysis, molar conductance, FTIR, UV–Vis absorption/fluorescence emission titration spectroscopy, PXRD and TGA/DTA studies, including DFT calculations. The cellular cytotoxicity of 1–3 when studied in HepG2 cancer cell line showed substantial cytotoxic effects, whereas no such cytotoxicity was observed when exposed to normal L6 skeletal muscle cell line. Thereafter, the signaling factors involved in the process of cytotoxicity in HepG2 cancer cells were investigated. Alteration of cytochrome c and Bcl-2 protein expression levels along with modulation of mitochondrial membrane potential (MMP) in the presence of 1–3, strongly suggested the possibility of activating mitochondria-mediated apoptotic pathway involved in halting the cancer cell propagation. However, when a comparative assessment on their bio-efficacies was made, 1 showed higher cytotoxicity, nuclear condensation, DNA binding and damage, ROS generation and lower rate of cell proliferation compared to 2 and 3 in HepG2 cell line, indicating that the anticancer activity of 1 is significantly higher than that of 2 and 3.