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Abstract
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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.
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