Ruthenium-arene complexes of curcumin: X-ray and density functional theory structure, synthesis, and spectroscopic characterization, in vitro antitumor activity, and DNA docking studies of (p-cymene)Ru(curcuminato)chloro

J Med Chem. 2012 Feb 9;55(3):1072-81. doi: 10.1021/jm200912j. Epub 2012 Jan 20.

Abstract

The in vitro antiproliferative activity of the title compound on five tumor cell lines shows preference for the colon-rectal tumor HCT116, IC(50) = 13.98 μM, followed by breast MCF7 (19.58 μM) and ovarian A2780 (23.38 μM) cell lines; human glioblastoma U-87 and lung carcinoma A549 are less sensitive. A commercial curcumin reagent, also containing demethoxy and bis-demethoxy curcumin, was used to synthesize the title compound, and so (p-cymene)Ru(demethoxy-curcuminato)chloro was also isolated and chemically characterized. The crystal structure of the title compound shows (1) the chlorine atom linking two neighboring complexes through H-bonds with two O(hydroxyl), forming an infinite two-step network; (2) significant twist in the curcuminato, 20° between the planes of the two phenyl rings. This was also seen in the docking of the Ru-complex onto a rich guanine B-DNA decamer, where a Ru-N7(guanine) interaction is detected. This Ru-N7(guanine) interaction is also seen with ESI-MS on a Ru-complex-guanosine derivative.

Publication types

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

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Coordination Complexes / chemical synthesis*
  • Coordination Complexes / chemistry
  • Coordination Complexes / pharmacology
  • Crystallography, X-Ray
  • Curcumin / chemical synthesis*
  • Curcumin / chemistry
  • Curcumin / pharmacology
  • Cymenes
  • DNA / chemistry*
  • Drug Screening Assays, Antitumor
  • Humans
  • Models, Molecular*
  • Molecular Structure
  • Ruthenium*
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Coordination Complexes
  • Cymenes
  • chloro(curcuminato)(p-cymene)ruthenium(II)
  • Ruthenium
  • DNA
  • Curcumin