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

J Inorg Biochem. 2023 Apr:241:112121. doi: 10.1016/j.jinorgbio.2023.112121. Epub 2023 Jan 4.

Abstract

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.

Keywords: Anthraquinone; Copper complexes; Cytotoxicity; DNA; N'N-heterocyclic ligands; Topoisomerase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Copper* / pharmacology
  • Crystallography, X-Ray
  • Dimethyl Sulfoxide
  • Heterocyclic Compounds*
  • Ligands
  • Protein Binding

Substances

  • Copper
  • Ligands
  • Dimethyl Sulfoxide
  • Heterocyclic Compounds