Effects of Cu(II) and Zn(II) coordination on the trypanocidal activities of curcuminoid-based ligands

Abstract

Four heteroleptic metal complexes with the general formula [M(L1-2)(phen)Cl] 1a-b, 2a-b, (M = Cu(II) or Zn(II), L = curcuminoid ligand and phen = phenanthroline) have been prepared from the reaction of the ligands in the presence of Et3N with CuCl2·2H2O or ZnCl2. Characterization by IR, 1H NMR and EPR spectroscopies, and X-ray diffraction analysis for 1b confirmed the proposed structures for the complexes. The curcuminoid ligand coordinates in a deprotonated form as an O,O chelate, with phen and chloride completing the coordination sphere of the metal. The cytotoxic effects of ligands (HL1, HL2, phen) and complexes (1a-b, 2a-b) on the amastigote form of Trypanosoma cruzi have been screened. All substances showed significant toxicity. The Zn(II) complexes 1b (IC50 = 0.47 μM, SI = 4.3) and 2b (IC50 = 0.40 μM, SI = 3.8) were the most potent compounds being more toxic and selective against the parasite than the ligands and the copper complexes, thus implying that the coordinating metal is important for the trypanocidal activity of the curcumin-based compounds.