Synthesis, Characterization, DNA Binding, Biological Evaluation, and Molecular Docking Approaches of Ternary Copper(II) Complexes Involving Ciprofloxacin With Glycine and Phenylalanine

Metal-based fluoroquinolone complexes are known as metalloantibiotics. Nowadays, these complexes represent a novel pathway to display a promising strategy to overcome antimicrobial resistance. Numerous studies have shown that metalloantibiotics can improve antimicrobial activity against antimicrobial resistance (AMR) compared to pure fluoroquinolones. With the purpose to evaluate the bio transformation and the mechanism of binding and the biological impact of metal-based antibiotics known to have high potency and low toxicity, in the present work two novel copper(II) complexes of fluoroquinolone antibiotic ciprofloxacin with two different amino acids with the formula [Cu (Cip)(Gly)Cl]·2H₂O (1) and [Cu (Cip)(Phe)Cl]·2H₂O (2), where Cip, Gly, and Phe are ciprofloxacin, glycine, and phenylalanine, respectively. The synthesized complexes have been characterized using elemental analysis, mass, and FTIR spectroscopy. The binding properties of the complexes (1) and (2) with calf thymus DNA (CT-DNA) and bovine serum albumin (BSA) were analyzed by UV-vis spectroscopy, and the calculated binding constants (K_b) for complexes (1) and (2) show a strong binding to CT-DNA (K_b value for complex (1) was 5.98 × 10³ M^-1 and for complex (2) was 1.5 × 10⁴M^-1 less strong binding affinity was reported for binding to BSA (K_b value for complex (1) was 1.98 × 10³M^-1 and for complex (2) was 8.3 × 10³M^-1). Thermal denaturation, gel electrophoresis, and viscosity measurements were performed to assess the binding interactions of complexes (1) and (2) with CT-DNA. The results indicate that both complexes exhibit an intercalative binding mode with CT-DNA. In addition, their antimicrobial, antitumor, antioxidant, cell cycle distribution (via flow cytometry), apoptosis, and antiviral activities were evaluated in vitro.