Cytotoxicity of ruthenium-N,N-disubstituted-N'-acylthioureas complexes

Mater Sci Eng C Mater Biol Appl. 2020 Oct:115:111106. doi: 10.1016/j.msec.2020.111106. Epub 2020 May 20.

Abstract

Five new complexes with general formula [Ru(Ln)(PP)(bipy)]PF6, where Ln = N,N'-dimethyl-N-Acyl thiourea, and P-P: 1,2-bis(diphenylphosphino)ethane (dppe) or 1,4-bis(diphenylphosphino)butane (dppb)) were synthesized and characterized by elemental analysis, molar conductivity, cyclic voltammetry, IR, NMR (1H, 13C{1H} and 31P{1H}), and single crystal X-ray diffractometry. The cytotoxicity of compounds against lung and breast tumor cell lines was significant, where two complexes, [Ru(L3)(bipy)(dppe)]PF6 (3) and [Ru(L3)(bipy)(dppb)]PF6 (6), were selected to evaluate changes in morphology, inhibition of migration and cell death in the MDA-MB-231 lineage. The complexes caused alterations in the cell morphology and were able to inhibit cell migration at the concentrations evaluated, induce the cell cycle arrested in the Sub-G1 phase, and induced cell death by apoptosis. All the complexes presented interaction with HSA, and the interaction studies with DNA suggested weak interactions, probably by the minor groove.

Keywords: Breast cancer; DNA interactions, apoptosis induction; Ruthenium complexes.

MeSH terms

  • A549 Cells
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Cell Cycle Checkpoints
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Survival / drug effects
  • Coordination Complexes / chemical synthesis*
  • Coordination Complexes / chemistry
  • Coordination Complexes / pharmacology
  • Crystallography, X-Ray
  • Humans
  • Molecular Conformation
  • Ruthenium / chemistry*
  • Thiourea / chemistry*

Substances

  • Antineoplastic Agents
  • Coordination Complexes
  • Ruthenium
  • Thiourea