Polynuclear ruthenium organometallic complexes containing a 1,3,5-triazine ligand: synthesis, DNA interaction, and biological activity

J Biol Inorg Chem. 2018 Dec;23(8):1205-1217. doi: 10.1007/s00775-018-1599-8. Epub 2018 Jul 23.

Abstract

It is now well established that ruthenium complexes are attractive alternatives to platinum-based anticancer agents. Most of the ruthenium compounds currently under investigation contain a single metal center. The synthesis of multinuclear analogues may provide access to novel complexes with enhanced biological activity. In this work, we have synthesized a set of three trinuclear complexes containing organometallic ruthenium fragments-(arene)RuCl-coordinated to a 2,4,6-tris(di-2-pyridylamino)-1,3,5-triazine core [(Arene = benzene (2), p-cymene (1), or hexamethylbenzene (3)]. The interaction of the complexes with DNA was extensively studied using a variety of biophysical probes as well as by molecular docking. The complexes bind strongly to DNA with apparent binding constants ranging from 2.20 to 4.79 × 104 M-1. The binding constants from electronic absorption titrations were an order of magnitude greater. The mode of binding to the nucleic acid was not definitively determined, but the evidence pointed to some kind of non-specific electrostatic interaction. None of the complexes displayed any significant antimicrobial activity against the organisms that were studied and exhibited anticancer activity only at high (> 100 μM) concentration.

Keywords: DNA; Molecular docking; Multinuclear; Organometallic; Ruthenium.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Coordination Complexes / chemical synthesis
  • Coordination Complexes / chemistry
  • Coordination Complexes / pharmacology*
  • DNA / chemistry*
  • Gram-Negative Bacteria / drug effects
  • Humans
  • Intercalating Agents / chemical synthesis
  • Intercalating Agents / chemistry
  • Intercalating Agents / pharmacology
  • Ligands
  • Methicillin-Resistant Staphylococcus aureus / drug effects
  • Microbial Sensitivity Tests
  • Molecular Docking Simulation
  • Molecular Structure
  • Ruthenium / chemistry*
  • Triazines / chemical synthesis
  • Triazines / chemistry
  • Triazines / pharmacology*

Substances

  • Anti-Bacterial Agents
  • Antineoplastic Agents
  • Coordination Complexes
  • Intercalating Agents
  • Ligands
  • Triazines
  • Ruthenium
  • DNA