New metallomacrocycles, 5-8, were synthesized by the coordination-driven self-assembly of thiophene-derived donor and arene ruthenium acceptors. Metallomacrocycles, 5-8, were fully characterized by 1H, 13C NMR spectroscopy, ESI-MS and elemental analysis. The molecular structure of macrocycle 8 was determined by single-crystal X-ray diffraction analysis. In addition, the anticancer activities of metallomacrocycles 5-8 were evaluated. The cytotoxic potential of macrocycle 7 was assessed using several cancer cells with different origins using the Tali assay and by quantitative western blotting. The results obtained support the notion that macrocycle 7 induces apoptotic cell death by activating intrinsic and extrinsic apoptosis pathways.