Half-sandwich Ru(II) complexes containing nitro-substituted furoylthiourea
ligands, bearing the general formula [(η6-
p-cymene)RuCl2(L)] (1-6) and [(η6-
p-cymene)RuCl(L)(PPh3)]+ (7--12), have been synthesized and characterized. In contrast to the spectroscopic data which revealed monodentate coordination of the
ligands to the Ru(II) ion via a "S" atom, single crystal X-ray structures revealed an unusual bidentate N, S coordination with the
metal center forming a four-membered ring. Interaction studies by absorption, emission, and viscosity measurements revealed intercalation of the Ru(II) complexes with calf thymus (CT)
DNA. The complexes showed good interactions with
bovine serum albumin (BSA) as well. Further, their cytotoxicity was explored exclusively against
breast cancer cells, namely, MCF-7, T47-D, and MDA-MB-231, wherein all of the complexes were found to display more pronounced activity than their
ligand counterparts. Complexes 7-12 bearing
triphenylphosphine displayed significant cytotoxicity, among which complex 12 showed IC50 values of 0.6 ± 0.9, 0.1 ± 0.8, and 0.1 ± 0.2 μM against MCF-7, T47-D, and MDA-MB-231 cell lines, respectively. The most active complexes were tested for their mode of cell death through staining assays, which confirmed apoptosis. The upregulation of apoptotic inducing and downregulation of apoptotic suppressing
proteins as inferred from the western blot analysis also corroborated the apoptotic mode of cell death. The active complexes effectively generated
reactive oxygen species (ROS) in MDA-MB-231 cells as analyzed from the
2',7'-dichlorofluorescein diacetate (
DCFH-DA) staining. Finally, in vivo studies of the highly active complexes (6 and 12) were performed on the mice model. Histological analyses revealed that treatment with these complexes at high doses of up to 8 mg/kg did not induce any visible damage to the tested organs.