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

Abstract

As novel promising anticancer candidates, the piano-stool type complexes of ruthenium, [RuCl(η⁶-p-cymene)(N,S-L_n)]PF₆, K₁-₄, were synthesized from the reaction of the substituted benzo[b]thiophene based thiosemicarbazone ligands (L_1-4) 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.