DNA binding and anti-cancer activity of redox-active heteroleptic piano-stool Ru(II), Rh(III), and Ir(III) complexes containing 4-(2-methoxypyridyl)phenyldipyrromethene

Inorg Chem. 2013 Apr 1;52(7):3687-98. doi: 10.1021/ic302196v. Epub 2013 Mar 11.

Abstract

The synthesis of four novel heteroleptic dipyrrinato complexes [(η(6)-arene)RuCl(2-pcdpm)] (η(6)-arene = C6H6, 1; C10H14, 2) and [(η(5)-C5Me5)MCl(2-pcdpm)] (M = Rh, 3; Ir, 4) containing a new chelating ligand 4-(2-methoxypyridyl)-phenyldipyrromethene (2-pcdpm) have been described. The complexes 1-4 have been fully characterized by various physicochemical techniques, namely, elemental analyses, spectral (ESI-MS, IR, (1)H, (13)C NMR, UV/vis) and electrochemical studies (cyclic voltammetry (CV) and differential pulse voltammetry (DPV)). Structures of 3 and 4 have been determined crystallographically. In vitro antiproliferative and cytotoxic activity of these complexes has been evaluated by trypan blue exclusion assay, cell morphology, apoptosis, acridine orange/ethidium bromide (AO/EtBr) fluorescence staining, and DNA fragmentation assay in Dalton lymphoma (DL) cell lines. Interaction of 1-4 with calf thymus DNA (CT DNA) has also been supported by absorption titration and electrochemical studies. Our results suggest that in vitro antitumor activity of 1-4 lies in the order 2 > 1 > 4 > 3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Cattle
  • Cell Line, Tumor
  • Chelating Agents / chemical synthesis*
  • Chelating Agents / pharmacology
  • Coordination Complexes / chemical synthesis*
  • Coordination Complexes / pharmacology
  • Crystallography, X-Ray
  • DNA / chemistry
  • DNA Fragmentation
  • Electrochemical Techniques
  • Humans
  • Iridium / chemistry
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Oxidation-Reduction
  • Porphobilinogen / analogs & derivatives*
  • Porphobilinogen / chemical synthesis
  • Porphobilinogen / pharmacology
  • Rhodium / chemistry
  • Ruthenium / chemistry

Substances

  • Antineoplastic Agents
  • Chelating Agents
  • Coordination Complexes
  • Iridium
  • Porphobilinogen
  • Ruthenium
  • DNA
  • calf thymus DNA
  • Rhodium