Antitumor copper(II) complexes with hydroxyanthraquinones and N,N-heterocyclic ligands

• Published in: Journal of inorganic biochemistry Vol. 241; p. 112121
• Main Authors: de Souza, Ívina P., de Melo, Ariane C.C., Rodrigues, Bernardo L., Bortoluzzi, Adailton, Poole, Simon, Molphy, Zara, McKee, Vickie, Kellett, Andrew, Fazzi, Rodrigo B., da Costa Ferreira, Ana M., Pereira-Maia, Elene C.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-04-2023
• Subjects: Anthraquinone; Copper - pharmacology; Copper complexes; Crystallography, X-Ray; Cytotoxicity; Dimethyl Sulfoxide; DNA; Heterocyclic Compounds; Ligands; N'N-heterocyclic ligands; Protein Binding; Topoisomerase; Topoisomerase; Cytotoxicity; Anthraquinone; DNA; N'N-heterocyclic ligands; Copper complexes
• ISSN: 0162-0134; 1873-3344
• DOI: 10.1016/j.jinorgbio.2023.112121

Five ternary copper(II) complexes, [Cu2(phen)2(L1)(ClO4)2] (1), [Cu2(phen)2(L1)(DMSO)2](PF6)2 (2), [Cu2(bpy)2(L1)(ClO4)2(H2O)2] (3), [Cu2(dmp)2(L1)(ClO4)2(H2O)2] (4), and [Cu(phen)(L2)]2(ClO4)2 (5), in which phen = 1,10-phenanthroline, bpy = 2,2′-bipyridine, dmp = 2,9-dimethyl-1,10-phenanthroline, H2L1 = 1,4-dihydroxyanthracene-9,10-dione and HL2 = 1-hydroxyanthracene-9,10-dione, DMSO = dimethylsulfoxide, were synthesized and fully characterized. Complex 2 was obtained through the substitution of perchlorate for DMSO. When two hydroxyquinone groups are present, L1 makes a bridge between two Cu(II) ions, which also bind two nitrogens of the respective diimine ligand. The compounds bind to calf thymus DNA and oxidatively cleave pUC19 DNA according to the following order of activity 1 > 4–5 > 3. Furthermore, complexes 1, 3, 4 and 5 inhibit topoisomerase-I activity and the growth of myelogenous leukemia cells with the IC50 values of 1.13, 10.60, 0.078, and 1.84 μmol L−1, respectively. Complexes 1 and 4 are the most active in cancer cells and in DNA cleavage.
Five ternary copper(II) complexes with hydroxyanthraquinones and N,Nheterocyclic ligands interact with DNA, inhibit topoisomerase activity and are highly cytotoxic to chronic myelogenous leukemia cells, with IC50 values in the range 0.08–10 μmol L−1. [Display omitted]
•Cu(II) complexes with hydroxyanthraquinones and diimines oxidatively cleave DNA.•Dihydroxyquinones bridge two Cu(II) ions also bound to two diimine nitrogens.•The complexes inhibit topoisomerase I activity at low concentrations.•Cytotoxicity to myelogenous leukemia cells is in the range 0.08–10 μM.