Synthesis, characterization, biomolecular interaction, cytotoxicity, and computational studies of quinoxaline-based platinum(II) complexes

Abstract

The combination of ninhydrin and o-phenylenediamine, followed by their reaction with a phenylhydrazine derivative produces quinoxaline-based ligands (L1 – L6). These ligands react with K2PtCl4 to form Pt(II) complexes (I – VI). The ligands and Pt(II) chelate were characterized through various spectroscopic and analytical techniques, like 1H NMR, 13C NMR, C, H, N-elemental analysis, IR spectroscopy, and mass spectrometry. DFT calculations were used to optimize the structures of metal complexes. To investigate the binding mode of complexes to CT-DNA/BSA, absorption titration, viscosity measurements, and molecular docking analysis were employed. The results indicated that the DNA binding mechanism involved intercalation. The antibacterial efficacy of the compounds was evaluated against five strains of bacteria. The lower minimum inhibitory concentration (MIC) of complexes suggests that they are more potent than quinoxaline-based ligands. The synthesized compounds were evaluated for cytotoxicity using brine shrimp. The LC50 values of ligands and complexes ranged from 7.64 to 11.45 μg/mL and 5.27 to 7.02 μg/mL, respectively. The capacity of the molecule to suppress cell proliferation using the MCF-7 cancer cell was tested, and the IC50 value was discovered to be comparable to that of a standard drug. Thus in this work, complexes demonstrated intercalation as the binding mode with CT-DNA/BSA and exhibited enhanced antibacterial efficacy compared to the ligands. The compounds also showed promising cytotoxicity against brine shrimp and MCF-7 cancer cells, with comparable IC50 values to a standard drug, indicating their potential as therapeutic agents.

Keywords

• Pt(II) complexes
• DNA binding
• DFT study
• Docking
• Anticancer