Synthesis DNA Protein Binding Nuclease Activity and Cytotoxicity Studies of Heteroleptic Copper II Complexes

Abstract

In recent years, transition metal complexes have become increasingly important in the development of metal-based anticancer agents due to their unique structure and accessible redox states in physiological conditions. Cisplatin, however, is effective against many types of cancer but has side effects including nephrotoxicity, ototoxicity, and neurotoxicity. To overcome the above drawbacks, researchers are perpetually motivated to discover biologically accessible metal-based anticancer agents. Among the transition metals, copper plays various roles in biological metabolisms such as pro-oxidant and antioxidant due to its redox properties, and human copper transporter 1 (hCtr1) as a copper membrane transporter 1 (CMT-1) carries copper inside the cells. Up to date, a few copper complexes have been entered into clinical trials; however, none of the complexes are approved for clinical use. Hence, a great deal of present thesis work involves the design, synthesis, and characterization of certain heteroleptic (mixed-ligand) copper(II) complexes of the type [Cu(PL)(CL)]+ / 2+ (1a-10a; 1b-7b; 1c-6c), where, PL is primary ligands such as quinoline (qp), quinoxaline (qc), quinazoline (qz), 4-phenyl-1-(pyridine-2-ylmethylene)thiosemicarbazone (HPTSC) and 4-phenyl-1 (ferrocene-2-ylmethylene)thiosemicarbazone (HFcTSC) and CL is co-ligands such as 2,2and#900;-bipyridine (bpy), 4,4and#900;-dimethyl-2,2and#900;- dipyridyl,1,10-phenanthroline (dmbpy), 1,10-phenanthroline (phen), 5,6-dimethyl-1,10- phenanthroline (5,6-dmp), 3,4,7,8-tetramethyl-1,10-phenanthroline (3,4,7,8-tmp), and dipyrido[3,2-f:2and#900;,3and#900;-h] quinoxaline (dpq) and determining the role of primary and co-ligands on their DNA/protein binding, nuclease activity and in vitro cytotoxicity. DNA and protein binding properties of the complexes have been monitored by interacting them with calfthymus (CT) DNA and BSA/HSA, respectively, using spectral and viscosity studies. newline