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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

  • Carlson Alexander
  • A. Nithyakumar
  • M. Wilson Bosco Paul
  • N. Arockia Samy
Original Paper
  • 219 Downloads

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.

Keywords

Cancer Anticancer complexes Imidazophenanthroline Platinum Ab initio and DFT computations 

Notes

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.

Compliance with ethical standards

Conflict of interest

There are no conflicts to declare.

Supplementary material

775_2018_1579_MOESM1_ESM.pdf (792 kb)
Supplementary material 1 (PDF 792 kb)

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Copyright information

© SBIC 2018

Authors and Affiliations

  1. 1.Department of ChemistryLoyola CollegeChennaiIndia
  2. 2.Department of ChemistrySacred Heart CollegeTirupatturIndia

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