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Platinum(II) complexes of imidazophenanthroline-based polypyridine ligands as potential anticancer agents: synthesis, characterization, in vitro cytotoxicity studies and a comparative ab initio, and DFT studies with cisplatin, carboplatin, and oxaliplatin

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Abstract

The synthesis of the platinum(II) complexes, [Pt(AIP)(bpy)](PF6)2 (1) and [Pt(PIP)(phen)](PF6)2 (2), of anthracene- and pyrene-conjugated imidazophenanthroline ligands and their in vitro cytotoxicity toward the fibroblast cells and the HeLa cell lines are reported. MTT assay demonstrates their cytotoxicity against the HeLa cell lines with the IC50 values of 1.35 and 1.56 µM, respectively, and the cytotoxicity profiles indicate that the HeLa cell lines show more activity than the fibroblast cells. Trypan blue assay highlights significant damage on the HeLa cell lines with a pronounced reduction on their clonogenicity. AO/EB staining shows marked morphologic signs of apoptosis in a dose-dependent manner and the LDH and DNA laddering assays also lend support to the cytotoxicity of the complexes. The molecular docking study reveals that the complexes interact with DNA through hydrogen bonding. The TD-DFT energy-optimized structures of the complexes show that the platinum(II) center has a slightly distorted square-planar geometry. The TD-DFT modelled LUMOs receive major contributions from the platinum d-orbitals, while the HOMOs are delocalized largely on the anthracenyl- and pyrenyl ligands, resulting in the LMCT transition at 352 nm. The structural, bonding, electronic, and optical properties of the complexes 1 and 2 reported in the present work and that of [Pt(AIP)(phen)](PF6)2 (3) and [Pt(PIP)(bpy)](PF6)2 (4), reported by us recently, and the approved drugs cisplatin, carboplatin, and oxaliplatin are described in the light of the optimized geometries, ΔEHOMO–LUMO, polarizability (α), hyperpolarizability (β), Mulliken negativities, and dipole moments computed from the ab initio and DFT computational studies.

Graphical abstract

The synthesis of Pt(II) complexes of anthracene- and pyrene-appended imidazophenanthroline ligands and their in vitro cytotoxicity against fibroblast cells and HeLa cell lines are reported. The DFT computational study of the complexes and cisplatin, carboplatin, and oxaliplatin are described in search of the ligand design features for the development of new Pt-drugs.

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Acknowledgements

Partial financial support to Carlson Alexander from Loyola College Research Park is gratefully acknowledged. The service rendered by the Sophisticated Analytical Instrumentation Facilities at IIT-Madras and Punjab and Jawaharlal Nehru Universities for recording ESI-TOF and MALDI-TOF mass spectra and NMR spectra is gratefully acknowledged. We thank Dr. Kavitha Sankaranarayanan, Ion Channel Biology Laboratory, AU-KBC Research Center, Anna University, Chennai, for carrying out the in vitro studies.

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  1. M. Wilson Bosco Paul

    Present address: Department of Chemistry, Sacred Heart College, Tirupattur, 635601, India

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  1. Department of Chemistry, Loyola College, Chennai, 600034, India

    Carlson Alexander, A. Nithyakumar, M. Wilson Bosco Paul & N. Arockia Samy

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Carlson Alexander is currently pursuing his Masters in Chemistry (M.Sc.) at The National Institute of Technology, Tiruchirappalli 620015, India.

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Alexander, C., Nithyakumar, A., Paul, M.W.B. et al. Platinum(II) complexes of imidazophenanthroline-based polypyridine ligands as potential anticancer agents: synthesis, characterization, in vitro cytotoxicity studies and a comparative ab initio, and DFT studies with cisplatin, carboplatin, and oxaliplatin. J Biol Inorg Chem 23, 833–848 (2018). https://doi.org/10.1007/s00775-018-1579-z

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