Copper pyrazole complexes as potential anticancer agents: Evaluation of cytotoxic response against cancer cells and their mechanistic action at the molecular level

This review-based study presents the anticancer potential of pyrazole-based copper complexes, aiming to evaluate their mechanistic action at the molecular level and find correlations between the biological activity and chemical structures of these complexes. Additionally, an attempt is made to provide evidence for the prospective anticancer applications of these compounds. The surveyed pyrazole-based copper complexes, with a variety of structural geometries and coordination numbers, exhibit a high potential for utilization as effective anticancer agents and alternatives to approved drugs with lower side effects. In vitro investigations reveal that the majority of the reported complexes display high antiproliferative activity, with some cases showing better cytotoxicity than approved standard drugs. However, various laboratory conditions, such as different incubation times for cytotoxicity determination, variations in the type and number of applied cell lines, and other influencing factors, can affect their inhibitory effects. Generally, the cell death mechanism of pyrazole-based copper complexes is synergistic and influenced by several parameters, including the oxidation state of the copper ion, various substitutions on the pyrazole derivative, the variety of donor chelating atoms, structural geometry, coordination number around the copper center, and dipole moment of the complexes. Possible cell death mechanisms include topo I, II (DNA topoisomerase I, II) inhibition, DNA cleavage, mitochondrial damage, arresting S and G2/M phases in the cell cycle, elevating intracellular oxidative stress, altering nuclear morphology, inducing endoplasmic reticulum stress, caspase-dependent and caspase-independent pathways, production of ROS (Reactive oxygen species) or peroxide-based pathways, and inducing apoptosis and paraptosis cell death mechanisms.