Synthesis and Characterization of Thiosemicarbazones- Ruthenium(II) Complexes: Anticancer Activity against Lung (A549) and Breast (MDA-MB-231) Cancers

Four novel thiosemicarbazone-ruthenium(II) complexes (Ru1–Ru4), with the general formula [Ru(L)(bipy)(dppb)]PF₆, were synthesized and characterized by CHN analysis, molar conductance, IR, UV-Vis, mass spectrometry, NMR, and cyclic voltammetry. The complexes contain morpholine-vanillin thiosemicarbazone ligands with different N-substituents. In vitro cytotoxicity studies demonstrated potent activity against A549 lung and MDA-MB-231 breast cancer cells, with IC₅₀ values of 2.10–7.40 μM and 1.30–2.60 μM, respectively, while exhibiting lower toxicity toward non-cancerous MRC-5 and MCF-10A cells. Ru4 showed the highest activity against MDA-MB-231 cells (IC₅₀ = 1.30 ± 0.03 μM; SI = 8.3). Morphological, clonogenic, live/dead, and wound-healing assays indicated apoptosis induction, growth inhibition, and reduced cell migration. DNA-binding studies revealed weak interaction with ct-DNA, whereas human serum albumin studies indicated a moderately spontaneous interaction predominantly stabilized by electrostatic and van der Waals forces, highlighting Ru4 as a promising anticancer candidate.