39 research outputs found
Ru(II)‑<i>p</i>‑Cymene Complexes of Furoylthiourea Ligands for Anticancer Applications against Breast Cancer Cells
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