Cyclometalated Complexes of Platinum and Palladium with <i>N</i>-(4-Chlorophenyl)-α-benzoylbenzylideneamine. <i>In Vitro</i> Cytostatic Activity, DNA Modification, and Interstrand Cross-Link Studies

Abstract

In the present paper we report the synthesis and structural IR and 1H and 13C NMR characterization of four platinum(II) and palladium(II) cyclometalated complexes of the formula [Pd(4-ClC6H4NC(COC6H5)C6H4)X]2, where X = OAc (2) or Cl (3), and [Pt(4-ClC6H4NC(COC6H5)C6H4)X]2, where X = Cl (4) or OAc (5). The acetate-bridged compounds 2 and 5 have an open-book structure. The chloro-bridged compounds 3 and 4 have an unfolded structure. Complex 2 crystallizes in the centrosymmetric triclinic space group P1̄, with Z = 2. Unit cell parameters are as follows: a = 11.765(3) Å, b = 12.862(4) Å, c = 15.022(5) Å, α = 84.08(2)°, β = 78.56(2)°, γ = 83.13(2)°. All these compounds were screened against MDA-MB 468 (breast carcinoma) and HL-60 (leukemic) tumor cells. The low IC50 values of compound 5 (1.05 μM) and of compound 4 (1.58 μM) against MDA-MB 468 and of 0.82 μM (5) and 1.37 μM (4) against HL-60 relative to cis-DDP (2.67 and 2.07 μM, respectively) and other cyclometalated compounds suggest that the synthesized compounds may be regarded as having potential antitumor properties. The data suggest that the antiproliferative activity of compound 5 may correlate with its covalent binding to DNA and the induction of important modifications on the helix.