DNA/bovine serum albumin binding and cytotoxicity of transition metal ternary complexes based on sulfamethazine and bromazepam drugs

Similar to the antibiotic mixing strategies, which depend on reducing the worth of diffusion of the resistant bacteria to new host, in this contribution, we explicit new mixed-ligand complexes of the type [M(SMZ)₂(BZM)] (M = Co(II), Ni(II) and Cu(II)) based on two drugs: sulfamethazine (SMZ) and bromazepam (BZM). The novelty aspect of the present work relies on combining two drugs in a single molecule via the synthesis of the ternary complexes. The ternary complexes were characterized by spectroscopic and analytical tools with the aid of the quantum chemical calculations. Copper(II) complex has the highest DNA intrinsic binding constant (2.20 × 10⁵ M⁻¹), induces extensively DNA cleavage compared to the other complexes, and exhibits the highest cytotoxicity (IC₅₀ = 0.67 μM) against human liver cancer cell line (HepG2). Exciting, Cu(II) compound exhibits no toxicity to the nonmalignant human foetal lung fibroblast (WI-38). Alternatively, the low cytotoxicity of the Co(II) complex correlates well with the high affinity of the compound to human serum albumin (K_b = 4.58 × 10⁵) compared to 1.93 × 10⁵ and 2.14 × 10⁵ M⁻¹ for Ni (II) and Cu (II) complexes, respectively.