Anticancer potency of copper(II) complexes of thiosemicarbazones

Being a structural and catalytic cofactor in a number of biological pathways, copper accumulates in tumors owing to selective permeability of the cancer cell membranes. Copper(II) ion forms the active centers in a large number of metalloproteins. The coordination of Schiff's base ligands to the metal ion results in the high extent of increase in anticancer activity. The copper(II) complexes can cleave DNA through oxidative and hydrolytic pathways, cell apoptosis via intrinsic reactive oxygen species (ROS) mediated mitochondrial pathway due to excessive production of ROS and hence, are found more active than Ni and Pt complexes. Flexible Cu(I/II) redox behavior helps the copper complexes to form more potent, clinically effective and less toxic copper based antiproliferative drugs of lower IC₅₀ value and higher growth inhibitory activity. Copper(II) complexes of thiosemicarbazones of Isatin, Pyridine, Benzoyl pyridine, Diacetyl/Dimethyl glyoxal, Acetophenone/Acetoacetanalide, Thiazole/Pyrazole, Quinoline, Carboxybenzaldehyde, Cinnamaldehyde/Cuminaldehyde, Citronellal, Chromone, Pyridoxal, 8-Ethyl-2-hydroxytricyclo (7.3.1.0^2,7) tridecan-13-one, Acyl Diazines, Naphthalene, Proline, 5-Formyluracil, 2-Hydroxy-8-propyltricyclo (7.3.1.0^2,7) tridecan-13-one, 9-cis-Retinal, Curcumin, Helicin (Salicylaldehyde-β-D-glucoside), Thiophene carboxaldehyde, Salicylaldehyde, Iminodiacetate, and 3-Formyl-4-hydroxy benzenesulfonic acid have been found to exhibit more anticancer activity toward HCT116, MCF7, A549, U937, HeLa, HepG2, SGC-7901, A2780 cell lines than that of their corresponding thiosemicarbazones and standard topoisomerase-II inhibitors.

Keywords: Anticancer activity; Cytotoxic activity; DNA cleavage; Reactive oxygen species (ROS); Thiosemicarbazone; Topoisomerase inhibition.