Synthesis, In Vitro Cytotoxic Evaluation, DFT Calculation and Molecular Docking for Novel Pyridine Derivative Platinum Complexes

Abstract

Novel pyridine derivative platinium complexes, ‐bis(2,4‐dimethylpyridine)dichloroplatinum(II), [PtCl2L12], bis(2‐amino‐5‐ chloropyridine)dichloroplatinum(II), [PtCl2L22] and bis(3‐amino‐2‐chloropyridine)dichloroplatinum(II), [PtCl2L32]‐ were synthesized and characterized via FT‐IR, UV‐Vis, 1H‐NMR, 13C‐NMR techniques and elemental analysis. The spectral assignment to structural data were corroborated via DFT/ MPW1PW91/LanL2DZ basic set. Vibrational transitions were conferred to the complexes by potential energy distribution analysis. Molecular electrostatic potential maps, frontier molecular orbitals and Mulliken charge distribution were calculated and the active regions of the molecules were determined. The interaction between 2ITO –a lung cancer protein‐ and the complexes was investigated by molecular docking. Protein‐ligand interactions established that the lung cancer cell interact more strongly with the [PtCl2L12] and the [PtCl2L22] complexes than the [PtCl2L32] complex. Cytotoxicity of the complexes against A549 and Beas‐2B normal lung cells via MTT colorimetric assay revealed that [PtCl2L12], [PtCl2L22] complexes most effective against lung cancer cell linesA549 and Beas‐2B over the incubation period of 24 h. These results suggest promising in‐vitro toxicity against the A549 and Beas‐2B that warrants furthest test in an animal model.