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

Five ternary copper(II) complexes, [Cu ₂ (phen) ₂ (L1)(ClO ₄ ) ₂ ] (1), [Cu ₂ (phen) ₂ (L1)(DMSO) ₂ ](PF6) ₂ (2), [Cu ₂ (bpy) ₂ (L1)(ClO ₄ ) ₂ (H ₂ O) ₂ ] (3), [Cu ₂ (dmp) ₂ (L1)(ClO ₄ ) ₂ (H ₂ O) ₂ ] (4), and [Cu(phen)(L2)] ₂ (ClO ₄ ) ₂ (5), in which phen = 1,10-phenanthroline, bpy = 2,2'-bipyridine, dmp = 2,9-dimethyl-1,10-phenanthroline, H ₂ L1 = 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 IC ₅₀ 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.
Competing Interests: Declaration of Competing Interest The authors confirm that there is no conflict of interest in Antitumor Copper(II) Complexes with Hydroxyanthraquinones and N,NHeterocyclic Ligands authored by Ívina P. de Souza, Ariane C.C. de Melo, Bernardo L. Rodrigues, Adailton Bortoluzzi, Zara Molphy, Vickie McKee, Andrew Kellett, Rodrigo B. Fazzi, Ana M. da Costa Ferreira, and myself, which we submit for publication on the Journal of Inorganic Biochemistry.
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