ROS -mediated anticancer response of potent copper(II) drug entities derived from S, O and N, N chelating donor scaffold: Single X-ray crystal diffraction and spectroscopic studies

• The structure of complexes 1 and 2 were thoroughly characterized. • The complexes 1 and 2 were synthesized with an idea of attaining a quick biologically Cu(II)/Cu(I) redox cycle. • The high in vitro cytotoxicity exhibited by five coordinated Cu(II) complex. • Mode of binding of 1 and 2 towards ct-DNA was studied. New Cu(II) anticancer drug entities derived from S, O, and N, N donor chelating scaffolds were synthesized and thoroughly characterized by various spectroscopic and single X-ray diffraction studies. The single X-ray crystal structure of 1 and 2 revealed a monoclinic and triclinic crystal system with space group C 2 / c and P -1, respectively. The biomolecular interaction studies of 1 and 2 with ct-DNA were carried out by employing a battery of biophysical techniques, viz., absorption, emission, circular dichroic, and electrochemical (CV) and corroborative results of these experiments demonstrated avid electrostatic binding via surface groove. The synthesized Cu(II) complexes showed high efficacy as ROS generators involving Cu(II)/Cu(I) redox-active pair as evidenced by cleavage assay in the presence of radical scavengers. The ROS generation in the presence of copper-based complexes is considered one of the most favorable cell death mechanisms for the inhibition of cancers. In vitro anticancer activity of 1 and 2 was, therefore, evaluated against a panel of five human cancer cell lines, namely MCF-7, MDA-MB-231, Hop-62, AW1356, and SiHa, and results of cytotoxicity demonstrated good anticancer response against all tested cancerous strains with GI 50 value <10 µM, except by 1 against MDA-MB-231, Hop-62 and AW1356 cell lines. Interestingly, 2 has displayed considerable cytotoxicity against MCF-7, Hop-62, and SiHa cancer cell lines even better than that of standard drug adriamycin. Furthermore, computational DFT studies validated the high binding efficacy and significant cytotoxicity of complex 2, which could be attributed to high positive charge density over the Cu(II) center. ROS induced DNA damage resulted Cell Death.