Anticancer potential of benzo[b]thiophene functionalized thiosemicarbazone ligands and their organoruthenium complexes

J Biol Inorg Chem. 2025 Feb;30(1):71-85. doi: 10.1007/s00775-024-02090-w. Epub 2024 Dec 31.

Abstract

As novel promising anticancer candidates, the piano-stool type complexes of ruthenium, [RuCl(η6-p-cymene)(N,S-Ln)]PF6, K1-4, were synthesized from the reaction of the substituted benzo[b]thiophene based thiosemicarbazone ligands (L1-4) with [{RuCl(η6-p-cymene)}2(μ-Cl)2]. All complexes were fully characterized using elemental analysis, and spectroscopic methods such as FT-IR and 1H NMR. The molecular masses of the complexes were proved by MALDI-TOF analysis. Single crystal X-ray diffraction study was employed in the structural elucidation of complex K1 which shows a distorted octahedral geometry around the Ru(II) ion. Furthermore, spectroscopic methods revealed that in all complexes the ligands are coordinated to the metal center in neutral thione form via N, S donors. In this study, the effect of all ligands, complexes and commercial drugs with a different concentration on the viability of OVCAR-3, A2780 and OSE cells were compared. In this comparison, the cytotoxicity of ruthenium (II) complexes on two ovarian cancer cell lines (human A2780 and human OVCAR-3) was evaluated. For this purpose, the resazurin assay was performed. Based on our studies, complex K2 showed the highest toxicity against OVCAR-3 and A2780 cells. The cytotoxic effect of K2 was found to be higher than that of the commercial anticancer agents Oxalpin and Carbodex, 1.8-34.7-fold for OVCAR-3 cells and 1.9-11.8-fold for A2780 cells, respectively. These results provide insight into the potential of ruthenium (II) complexes as a cytotoxic agent for the treatment of ovarian cancer, particularly for primary tumors.

Keywords: Anticarcinogenic activity; Crystal structure; Organoruthenium-arene complexes; Ovarian cancer cell lines; Thiosemicarbazone.

MeSH terms

  • Antineoplastic Agents* / chemical synthesis
  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Coordination Complexes* / chemical synthesis
  • Coordination Complexes* / chemistry
  • Coordination Complexes* / pharmacology
  • Crystallography, X-Ray
  • Drug Screening Assays, Antitumor
  • Humans
  • Ligands
  • Models, Molecular
  • Molecular Structure
  • Ruthenium* / chemistry
  • Ruthenium* / pharmacology
  • Structure-Activity Relationship
  • Thiophenes* / chemistry
  • Thiophenes* / pharmacology
  • Thiosemicarbazones* / chemistry
  • Thiosemicarbazones* / pharmacology

Substances

  • Thiosemicarbazones
  • Antineoplastic Agents
  • Ruthenium
  • Ligands
  • Thiophenes
  • Coordination Complexes