New organoruthenium complexes with bioactive thiosemicarbazones as co-ligands: potential anti-trypanosomal agents

Dalton Trans. 2012 Feb 7;41(5):1534-43. doi: 10.1039/c1dt11519g. Epub 2011 Dec 2.

Abstract

In the search for new therapeutic tools against neglected diseases produced by trypanosomatid parasites, and particularly against African Trypanosomiasis, whose etiological agent is Trypanosoma brucei, organoruthenium compounds with bioactive nitrofuran containing thiosemicarbazones (L) as co-ligands were obtained. Four ruthenium(II) complexes with the formula [Ru(2)(p-cymene)(2)(L)(2)]X(2), where X = Cl or PF(6), were synthesized and the crystal structures of two of them were solved by X-ray diffraction methods. Two of the complexes show significant in vitro growth inhibition activity against Trypanosoma brucei brucei and are highly selective towards trypanosomal cells with respect to mammalian cells (J774 murine macrophages). These promising results make the title organoruthenium compounds good lead candidates for further developments towards potential antitrypanosomal organometallic drugs.

Publication types

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

MeSH terms

  • Animals
  • Cattle
  • Cell Line
  • Crystallography, X-Ray
  • DNA / metabolism
  • Humans
  • Ligands
  • Macrophages / drug effects
  • Mice
  • Models, Molecular
  • Organoselenium Compounds / chemistry*
  • Organoselenium Compounds / pharmacology*
  • Trypanocidal Agents / chemistry*
  • Trypanocidal Agents / pharmacology*
  • Trypanosoma brucei brucei / drug effects*
  • Trypanosomiasis, African / drug therapy

Substances

  • Ligands
  • Organoselenium Compounds
  • Trypanocidal Agents
  • DNA
  • calf thymus DNA