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Half-sandwich Ru(II) complexes containing nitro-substituted furoylthiourea ligands, bearing the general formula [(η 6 -p-cymene)RuCl 2 (L)] (1−6) and [(η 6 -p-cymene)RuCl(L)(PPh 3 )] + (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 IC 50 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.

We report the synthesis of five new Cu(I) acylthiourea complexes (C1–C5) bearing the general formula [Cu(L‐R)Cl (PPh3)2] [L = monodentate acylthiourea ligand, R = C6H5 (L1), C6H4CH3(o) (L2), C6H4OCH2CH3(p) (L3), C10H7 (L4) or C6H4Cl(p) (L5)]. All the complexes were characterized by analytical and spectroscopic tools. The complexes (C1–C5) exhibited a distorted tetrahedral geometry as inferred from the single crystal X‐ray diffraction study. The complexes were subjected to interact with the biomolecules (calf thymus [CT] DNA/bovine serum albumin [BSA]); the one bearing naphthyl substituent (C4) exhibited the highest binding efficacy. Further, anticancer activity of the complexes was studied exclusively against breast cancer cell lines, namely, MCF7, T47D, and MDA MB 231. Complex C4 was found to be highly cytotoxic on the three cancer cell lines with the IC50 values of 0.75, 0.75, and 0.68 μM, respectively. Conveniently, the complexes displayed fourfold less toxicity against the normal MCF10a human breast cells. The ability of complex C4 to induce apoptosis was analyzed by acridine orange/ethidium bromide (AO/EB) and Hoechst 33258 staining assays. Furthermore, it was found that complex C4 induced apoptosis via reactive oxygen species (ROS)‐mediated mitochondrial signaling pathway. Confocal fluorescence images of the cells subjected to lyso and mitotracker staining assays revealed that complex C4 was primarily localized on the mitochondria, and finally, Western blot analysis also confirmed the apoptosis induced by complex C4 in the MDA MB 231 cancer cells.