Bioactive ruthenium(II)-arene complexes containing modified 18β-glycyrrhetinic acid ligands

J Inorg Biochem. 2018 May:182:194-199. doi: 10.1016/j.jinorgbio.2018.02.004. Epub 2018 Feb 21.

Abstract

Metal-arene complexes containing bioactive natural-product derived ligands can have new and unusual properties. We report the synthesis, characterization and antiproliferative activity of two new Ru(II) arene complexes with imidazole (dichlorido complex 1) or bipyridyl (chlorido complex 2) ligands conjugated to 18β-glycyrrhetinic acid, an active triterpenoid metabolite of Glycyrrhiza glabra. In general, the conjugated ligands and complexes showed only moderate activity against HeLa (cervical), MCF-7 (breast) and A2780 (ovarian) cancer cells, although the activity of complex 2 in the former two cell lines approached that of the drug cisplatin. Complex 2 (in contrast to complex 1) also exhibited significant activity towards both Gram-positive S. aureus and Gram-negative E. coil bacteria. Complex 2 can induce condensation of DNA and enhances the generation of intracellular reactive oxygen species (ROS). The conjugation of natural products to ligands in organometallic half-sandwich complexes provides a strategy to enhance their biological activities.

Keywords: 18β-Glycyrrhetinic acid; Anticancer; Ru(II) arene complexes.

Publication types

  • Research Support, Non-U.S. Gov't

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
  • Cell Proliferation / drug effects
  • Cisplatin / pharmacology
  • Escherichia coli / drug effects
  • Glycyrrhetinic Acid / analogs & derivatives*
  • Glycyrrhetinic Acid / chemistry
  • HeLa Cells
  • Humans
  • Ligands
  • MCF-7 Cells
  • Molecular Structure
  • Organometallic Compounds / chemical synthesis
  • Organometallic Compounds / chemistry
  • Organometallic Compounds / pharmacology
  • Reactive Oxygen Species / metabolism
  • Ruthenium
  • Staphylococcus aureus / drug effects
  • Structure-Activity Relationship

Substances

  • Anti-Bacterial Agents
  • Antineoplastic Agents
  • Ligands
  • Organometallic Compounds
  • Reactive Oxygen Species
  • 18alpha-glycyrrhetinic acid
  • Ruthenium
  • Glycyrrhetinic Acid
  • Cisplatin