Publication in International Journal of Molecular Sciences

Copper(II) Complexes Containing Natural Flavonoid Pomiferin Show Considerable In Vitro Cytotoxicity and Anti-inflammatory Effects


Authors: Ján Vančo, Jan Hošek, Tomáš Malina, Zdeněk Dvořák and Zdeněk Trávníček



A series of five new heteroleptic copper(II) pomiferin-containing complexes were prepared and thoroughly characterized. The complexes were found as effective antiproliferative agents revealing significant in vitro cytotoxicity against a panel human cancer cell lines (MCF-7, HOS, A549, PC-3, A2780, A2780R, Caco-2 and THP-1), with the IC50 values of 2.2–13.0 μM for the best performing complexes 3 and 5. Moreover, the complexes showed relatively low toxicity on healthy human hepatocytes, with IC50 > 100 μM. In addition to that, the results following from an Annexin V/PI apoptosis assay, induction of intracellular reactive oxygen species (ROS) production, perturbation of mitochondrial membrane potential and nuclease mimicking activity revealed their ability to induce the processes leading to the destruction of intracellular molecules of life and subsequent cell death, dominantly via the initiation or progression of oxidative stress. On the other hand, the complexes showed an ability to inhibit the inflammation-related signalling pathways (NF-κB/AP-1 activity, NF-κB translocation and TNF-αsecretion), thus rendering the tested complexes as effective anti-inflammatory substances. Overall, the results showed significant biological potential of the studied compounds and revealed that copper(II) complexes, involving the naturally occurring ligand pomiferin with intrinsic biological activities, deserve to be studied deeper and in greater detail in the future.