Tetranuclear cubane Cu₄O₄ complexes as prospective anticancer agents: Design, synthesis, structural elucidation, magnetism, computational and cytotoxicity studies

Two new homometallic Cu₄O₄ cubane clusters 1 and 2 have been synthesized by self-assembly of copper(II) acetate and ligand, 2-[(2-Hydroxy-3-methoxy-benzylidene)-amino]-2-hydroxymethyl-propane-1,3-diol (H₄L) and characterized thoroughly by various spectroscopic techniques and single crystal X-ray diffraction analysis. Temperature-dependent magnetic susceptibility measurements have been performed to elucidate the antiferromagnetic and ferromagnetic nature in Cu₄O₄ clusters 1 and 2, respectively. In vitro DNA binding studies of cubane clusters were carried out by employing optical spectroscopic techniques. Gel electrophoretic mobility assay performed to examine the nuclease activity of the complexes 1 and 2 with pBR322 DNA, and results revealed oxidative DNA cleavage via reactive oxygen species (ROS) species viz., O₂^[rad]‾, ¹O₂, etc. In vitro cell proliferation via MTT assay was studied to calculate the cytotoxicity of complexes 1 and 2. The IC₅₀ evaluated were ∼20 µM in MCF-7 (Breast) and ∼30–35 µM in HepG2 (Liver) cancer cell lines. Additionally, in the presence of 1 and 2, ROS and TBARS (Thiobarbituric acid reactive substance) levels amplified significantly, coupled with GSH (glutathione) levels in cancer lines. Hence, the results exhibited the major role of ROS in apoptosis induced by 1 and 2 clusters and validate their prospective to be efficient anticancer drug entities.