Cadmium(ii) complexes with a 4-acyl pyrazolone derivative and co-ligands: crystal structures and antitumor activity

Abstract

Three cadmium(II) complexes, [Cd(HL)₂(CH₃OH)₂]·(CH₃OH) (1), [Cd(HL)₂(bpy)]·(CH₃OH)₂ (2), and [Cd(HL)₂(phen)]·(CH₃OH)_1.5 (3), (where H₂L = N-(1-phenyl-3-methyl-4-(4-chlorobenzoyl)-5-pyrazolone)-2-thiophenecarboxylic acid hydrazide, bpy = 2,2′-bipyridine, phen = 1,10-phenanthroline) have been synthesized and characterized. Single crystal X-ray diffraction analyses indicated that complexes 1–3 exhibit mononuclear octahedral geometry. The spectrophotometric analyses showed that these complexes could bind with herring sperm DNA and bovine serum albumin (BSA). The intrinsic binding constants to HS-DNA were 2.46 × 10⁴ M⁻¹, 2.64 × 10⁴ M⁻¹, and 4.41 × 10⁴ M⁻¹, and the quenching constants to BSA were 1.23 × 10⁶ M⁻¹, 1.85 × 10⁶ M⁻¹, and 2.17 × 10⁶ M⁻¹ for the complexes 1–3, respectively. The complexes have higher cytotoxic activities against HeLa and Eca-109 tumor cells than that of the ligand and cisplatin. Complex 3 shows the highest cytotoxicity for both HeLa and Eca-109, and the IC₅₀ values are 3.35 ± 0.2 μg mL⁻¹ and 7.41 ± 0.07 μg mL⁻¹, respectively. When compared with our previous work, IC₅₀ value of the reported complex CdC₂₀H₁₈N₄O₃ to Eca-109 cells is 14.18 μg mL⁻¹. We further found that complex 3 inhibits the growth of HeLa cells by inducing apoptosis and arresting the cell cycle during the G0/G1 phase. These results suggest that complex 3 is a potential antitumor drug.