Appended Aromatic Moieties Determine the Cytotoxicity of Neutral Cyclometalated Platinum(II) Complexes Derived from 2-(2-Pyridyl)benzimidazole

Inorg Chem. 2020 Apr 6;59(7):4961-4971. doi: 10.1021/acs.inorgchem.0c00219. Epub 2020 Mar 17.

Abstract

A new family of neutral chiral cyclometalated platinum(II) complexes with formula [Pt(κ2-(C^N))Cl(κ1-(L))], where (C^N) = 2-phenylpyridinate and (L) = 2-(2-pyridyl)benzimidazole (L1) or (N-(CH2)-Ar-(2-(2-pyridyl)benzimidazole) ligands; (Ar = phenyl (L2), naphthyl (L3), pyrenyl (L4)), have been synthesized and completely characterized. The unexpected κ1 coordination mode of the 2-(2-pyridyl)benzimidazole-derived ligands has been confirmed by spectroscopic techniques and X-ray diffraction. The aromatic moieties on the ligands in the new platinum(II) complexes have a remarkable influence on the cytotoxicity and in the binding mode to DNA. [Pt-L1]-[Pt-L4] complexes internalized more than cisplatin in the SW480 cancer cells even though only [Pt-L1] and [Pt-L2] display high cytotoxicity. 1H NMR and 13P{1H}NMR pointed out that [Pt-L1] and [Pt-L2] complexes bind covalently to dGMP, while the electrophoresis assays and CD experiments indicate that only [Pt-L2] is able to covalently interact with DNA, inducing the same conformational changes in the plasmid DNA as cisplatin. Although the complex [Pt-L4] intercalates into DNA, probably through the pyrenyl moiety, no biological activity is observed.

MeSH terms

  • Acinetobacter baumannii / drug effects
  • Animals
  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / metabolism
  • Anti-Bacterial Agents / pharmacology*
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology*
  • Benzimidazoles / chemical synthesis
  • Benzimidazoles / metabolism
  • Benzimidazoles / pharmacology*
  • Cattle
  • Cell Line, Tumor
  • Coordination Complexes / chemical synthesis
  • Coordination Complexes / metabolism
  • Coordination Complexes / pharmacology*
  • DNA / chemistry
  • DNA / metabolism
  • Drug Screening Assays, Antitumor
  • Enterococcus faecium / drug effects
  • Humans
  • Ligands
  • Platinum / chemistry
  • Pseudomonas aeruginosa / drug effects
  • Staphylococcus aureus / drug effects

Substances

  • Anti-Bacterial Agents
  • Antineoplastic Agents
  • Benzimidazoles
  • Coordination Complexes
  • Ligands
  • Platinum
  • DNA
  • calf thymus DNA