DNA and BSA binding and cytotoxic properties of copper(ii) and iron(iii) complexes with arylhydrazone of ethyl 2-cyanoacetate or formazan ligands

Abstract

Several known water soluble [Cu(1κN,O²:2κO-HL¹)(S)]₂ [S = CH₃OH (1), (CH₃)₂NCHO (2)] and [Cu(κN-HL¹)(en)₂]·CH₃OH·H₂O (3) Cu^II complexes were prepared by reaction of Cu^II nitrate hydrate with the new (E/Z)-4-(2-(1-cyano-2-ethoxy-2-oxoethylidene)hydrazinyl)-3-hydroxybenzoic acid (H₃L¹), in the presence (for 3) or absence (for 1 and 2) of ethylenediamine (en), while the Fe^III complex [Fe(κN³-HL²)₂] (4) was synthesized by treatment of iron(III) chloride hexahydrate with the new (1E,1E)-N′,2-di(1H-1,2,4-triazol-3-yl)diazenecarbohydrazonoyl cyanide (H₃L²). The interaction of calf thymus DNA (CT DNA) and bovine serum albumin (BSA protein) with complexes 1–4 has been investigated by absorption and fluorescence titration methods. The observed DNA binding constants, number of DNA binding sites (s ≤ 1) for the complexes and viscosity data suggest the intercalative mode of binding to CT DNA. All the complexes show good binding propensity to the BSA protein, giving K_BSA values of 0.97(±0.10) × 10⁶ (1), 1.19(±0.09) × 10⁶ (2), 0.50(±0.01) × 10⁶ (3) and 1.06(±0.08) × 10⁶ M⁻¹ (4). An in vitro anti-proliferative study establishes the anticancer potency of complexes 1–4 and cisplatin against the human cervical (HeLa) and breast (MCF7) cancer cell lines; noncancer breast epithelial (MCF10) cells were also investigated. The observed IC₅₀ values of complexes 1 (8.3, 11.9 and 44.8 μM), 2 (7.0, 7.1 and 35.6 μM), 3 (18.1, 20.4 and 58.8 μM), 4 (13.2, 15.1 and 79.4 μM) and cisplatin (4.02, 3.42 and 89.5 μM) against the HeLa, MCF7 and MCF-10a cells, respectively, suggest that 2 can be explored further as a potential anticancer drug.