Potent drug candidature of copper-coordinated metallodrug: Experimental study, spectroscopic insights, anticancer activity, apoptosis analysis, cell cycle, theoretical calculations, and molecular docking studies

The biological properties of the thiocarbohydrazone, pyrazole, and copper ions are well-known, thus copper complexes incorporated with pyrazole-thiocarbohydrazone hybrid ligands have potential medical applications. In this study, copper complex [Cu(PMT)(2)(Cl)(2)] derived from pyrazole-thiocarbohydrazone hybrid chelator (PMT) was successfully synthesized. With the help of several fundamental techniques, including elemental and thermal studies, molar conductivity, and magnetic moment measurements, the structure and coordination behavior of the PMT chelator and its Cu(PMT) nanocomplex were examined. In addition, records of ESR, FT-IR, and UV-Vis spectroscopy were obtained. The powder X-ray diffraction data has identified significant information about the crystalline forms of the Cu(PMT) chelate. The findings demonstrated that producing octahedral, mono-species of chelate and chelation occurs through the N, and S donor sites of neutral chelator. The cytotoxicity assessment of the PMT and its Cu(PMT) chelate was further evaluated against human ovary cancer cells (SKOV3), human breast cancer cells (MCF-7), and human colon cancer cells (HCT116) by using SRB assay. The Cu(PMT) chelate displayed promising results regarding standard doxorubicin. Furthermore, the apoptosis analysis of the Cu(PMT) chelate strongly induced the late-apoptotic cell population against the tested cancer cells. Also, the cell-cycle distribution of the Cu(PMT) complex arrests cell proliferation at the G1, S, and G2 phases. PMT and its Cu(PMT) were also studied using computational simulations and the DFT approach. Different chemical quantum parameters were determined from the optimized structure. The interaction between copper chelate and the CDK8 kinase active site was examined using docking studies.