Synthesis and anticancer activity of carbosilane metallodendrimers based on arene ruthenium(ii) complexes

Dalton Trans. 2016 Apr 28;45(16):7049-66. doi: 10.1039/c6dt00465b.

Abstract

A series of new organometallic carbosilane dendrimers (first and second generation) and the corresponding non-dendritic mononuclear based on ruthenium arene fragments are described. The metallodendrimers were prepared by reactions of the precursor [Ru(η(6)-p-cymene)Cl2]2 with carbosilane dendrimers functionalized with N-donor monodentate ligands such as NH2- and pyridine, or with N,O-, N,N-chelating imine ligands. While the dendrimer precursors are insoluble in DMSO or water, novel metallodendrimers are soluble in DMSO and some of them are even highly soluble in water. The molecular structure of the "Ru-NH2" mononuclear compound (zero generation) was determined by single-crystal X-ray crystallography. The cytotoxicity activity of these dendritic structures was evaluated in several human cancer cell lines and compared with that of the corresponding mononuclear ruthenium complexes. Most compounds display significant cytotoxic activities in the low micromolar range with the first generation ruthenium dendrimers being the most active compounds. The cell death type for selected compounds has been studied as well as their reactivity towards relevant biomolecules such as DNA, Human Serum Albumin (HSA) and Cathepsin-B. All the data point to a mode of action different from that of cisplatin for most complexes. First generation ruthenium dendrimers inhibit Cathepsin-B, which may suggest potential antimetastatic properties of these compounds.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology*
  • Cathepsin B / antagonists & inhibitors
  • Cell Death / drug effects
  • Cell Line, Tumor
  • Chemistry Techniques, Synthetic
  • DNA / metabolism
  • Dendrimers / chemistry*
  • Humans
  • Ligands
  • Organometallic Compounds / chemical synthesis*
  • Organometallic Compounds / chemistry
  • Organometallic Compounds / metabolism
  • Organometallic Compounds / pharmacology*
  • Ruthenium / chemistry*
  • Serum Albumin / metabolism
  • Silanes / chemistry*

Substances

  • Antineoplastic Agents
  • Dendrimers
  • Ligands
  • Organometallic Compounds
  • Serum Albumin
  • Silanes
  • carbosilane
  • Ruthenium
  • DNA
  • Cathepsin B