Design and characterization of highly in vitro antitumor active ternary copper(II) complexes containing 2′-hydroxychalcone ligands

• New group of 8 Casiopeínas®-like complexes involving chalcone ligands is reported.
• Significant in vitro cytotoxicity against 10 human cancer cell lines was found.
• Three complexes were able to overcome the resistance of A2780R cells to cisplatin.
• Complexes showed good selectivity towards cancer cells as compared to hepatocytes.
• Complexes have high affinity to biomolecules and ability to oxidatively cleave DNA.

A series of innovative copper(II) complexes of the general composition [Cu(Ln)(phen)]NO3 (1–8; phen = 1,10-phenanthroline), involving 2′-hydroxychalcone {(E)-1-(2′-hydroxyphenyl)-3-phenylprop-2-en-1-one} derivatives (HLn) was synthesized, thoroughly characterized and screened for in vitro cytotoxicity against a panel of ten human cancer cell lines. The most promising results were achieved for complex 2 with the best IC50 value of 1.1 ± 0.7 μM (against A2780 cell line). The toxicity testing on a primary culture of human hepatocytes (HH) revealed that complex 2 is the least toxic from the whole series with the IC50 value of 63.7 μM. The complexes were shown to be able to efficaciously cleave pUC19 plasmid DNA as well as intercalate into calf thymus DNA with the same affinity and efficacy as ethidium bromide and interact by the ligand exchange mechanism with l-cysteine at physiological concentration levels.

1,10-Phenanthroline-copper(II) complexes, involving the 2′-hydroxychalcone ligands, were prepared, characterized, and screened for in vitro antitumor activity. The complexes were found to be highly cytotoxic, showing the best IC50 value of 1.1 μM (against A2780 cells), and their ability to interact and damage biomolecules has been demonstrated on selected model systems.Figure optionsDownload as PowerPoint slide