Karim, AmirAmirKarimMalekshah, Rahimeh EshaghiRahimeh EshaghiMalekshahShu, En-DeEn-DeShuJebiti HaribabuChu, Yu-TingYu-TingChuChien, Ching-MingChing-MingChienHsu, Sodio C. N.Sodio C. N.Hsu2026-07-072026-07-072026-06INORGANIC CHEMISTRY COMMUNICATIONS, 188, 116514 (2026). https://doi.org/10.1016/j.inoche.2026.1165141387-70031879-0259https://hdl.handle.net/20.500.12740/24691A series of piano-stool ruthenium(II)-p-cymene complexes featuring an acylthiourea ligand in monodentate (S-coordinated), bidentate (S,N-chelated), and azido auxiliary forms were synthesized and comprehensively characterized by FT-IR, UV-vis, ESI-Mass, 1H NMR, and 13C NMR spectroscopy, elemental analysis, and single-crystal X-ray diffraction. All complexes exhibit the characteristic piano-stool geometry, with distinct coordination environments influencing Ru-ligand bond lengths and molecular symmetry. Stability studies in DMSO-d6 showed excellent stability for the monodentate complex, partial reversibility for the bidentate species, and minor solvolysis for the azido derivative. In vitro cytotoxicity was evaluated against human melanoma (A375 & A2058) and breast cancer (MCF-7 & MDA-MB-231) cell lines, as well as noncancerous (ARPE-19 & MCF-10A) cells, using the MTT assay. The neutral monodentate complex exhibited the highest potency, particularly against melanoma cells, while bidentate and azido complexes showed moderate selectivity. Notably, to the best of our knowledge, this is the first report describing the anticancer evaluation of a Ru(II)-p-cymene complex incorporating both an acylthiourea ligand and an azido ancillary ligand. Frontier molecular orbital analysis and ADMET predictions supported the observed structure-activity relationships, with the smallest HOMO-LUMO gap and optimal lipophilicity correlating with enhanced activity for the monodentate species. Docking studies revealed that complex 1 exhibits the strongest DNA binding affinity (-72.61 k.cal.mol-1) among the complexes. These findings highlight the critical role of coordination mode and auxiliary ligands in modulating the anticancer properties of Ru(II)-p-cymene acylthiourea complexes.AcylthioureaAzido ligandRu-p-cymeneCoordination modesAnticancer activityIn-silico studiesInfluence of coordination mode and auxiliary ligands on the anticancer activities of ruthenium(II)-p-cymene acylthiourea complexesArticulohttps://doi.org/10.1016/j.inoche.2026.116514