3 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
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
Water-Soluble Mono- and Binuclear Ru(η<sup>6</sup>‑<i>p</i>‑cymene) Complexes Containing Indole Thiosemicarbazones: Synthesis, DFT Modeling, Biomolecular Interactions, and <i>In Vitro</i> Anticancer Activity through Apoptosis
Indole
thiosemicarbazone ligands were prepared from indole-3-carboxaldehyde
and <i>N</i>-(un)Âsubstituted thiosemicarbazide. The RuÂ(η<sup>6</sup>-<i>p</i>-cymene) complexes [RuÂ(η<sup>6</sup>-<i>p</i>-cymene)Â(HL1)ÂCl]Cl (<b>1</b>) and [RuÂ(η<sup>6</sup>-<i>p</i>-cymene)Â(L2)]<sub>2</sub>Cl<sub>2</sub> (<b>2*</b>) were exclusively synthesized from thiosemicarbazone
(TSC) ligands HL1 and HL2, and [RuCl<sub>2</sub>(<i>p-</i>cymene)]<sub>2</sub>. The compounds were characterized by analytical
and various spectroscopic (electronic, FT-IR, 1D/2D NMR, and mass)
tools. The exact structures of the compounds (HL1, HL2, <b>1</b>, and <b>2*</b>) were confirmed by single-crystal X-ray diffraction
technique. In complexes <b>1</b> and <b>2*</b>, the ligand
coordinated in a bidentate neutral (<b>1</b>)/monobasic (<b>2*</b>) fashion to form a five-membered ring. The complexes showed
a piano-stool geometry around the Ru ion. While <b>2*</b> existed
as a dimer, <b>1</b> existed as a monomer, and this was well
explained through free energy, bond parameter, and charge values computed
at the B3LYP/SDD level. The intercalative binding mode of the complexes
with calf thymus DNA (CT DNA) was revealed by spectroscopic and viscometric
studies. The DNA (pUC19 and pBR322 DNA) cleavage ability of these
complexes evaluated by an agarose gel electrophoresis method confirmed
significant DNA cleavage activity. Further, the interaction of the
complexes with bovine serum albumin (BSA) was investigated using spectroscopic
methods, which disclosed that the complexes could bind strongly with
BSA. A hemolysis study with human erythrocytes revealed blood biocompatibility
of the complexes. The <i>in vitro</i> anticancer activity
of the compounds (HL1, HL2, <b>1</b>, and <b>2*</b>) was
screened against two cancer cell lines (A549 and HepG-2) and one normal
cell line (L929). Interestingly, the binuclear complex <b>2*</b> showed superior activity with IC<sub>50</sub> = 11.5 ÎĽM, which
was lower than that of cisplatin against the A549 cancer cell line.
The activity of the same complex (IC<sub>50</sub> = 35.3 ÎĽM)
was inferior to that of cisplatin in the HepG-2 cancer cell line.
Further, the apoptosis mode of cell death in the cancer cell line
was confirmed by using confocal microscopy and DNA fragmentation analysis