Eight new organometallic Ru(II)–arene
complexes of the type
[RuCl
2
(η
6
-arene)(η
1
-
S
-aroylthiourea)] (arene =
p
-cymene or
benzene) were synthesized in order to evaluate the effect of the arene
moiety and the substituent of the aroylthiourea ligand on the cytotoxicity
of the complexes. The ligands (L1 and L2) and complexes (
1–8
) were characterized using analytical and spectroscopic (UV–visible,
infrared,
1
H NMR,
13
C NMR, and mass) methods.
The structure of the ligands (L1 and L2) and complexes (
1
and
3–6
) was obtained from single-crystal X-ray
diffraction studies. The cytotoxicity of the complexes was evaluated
against four different cancer cell lines: MCF-7 (breast), COLO 205
(colon), A549 (lung), and IMR-32 (neuroblastoma). All the complexes
showed good cytotoxicity and the highest was in the IMR-32 cell line,
which articulates the specificity of these complexes toward the IMR-32
cancer cell line. The complexes
5
,
7
, and
8
exhibited remarkable cytotoxicity in the entire cancer cell
lines tested, which was comparable with the standard drug, cisplatin.
The anticancer mechanism of the complexes
3
and
7
in IMR-32 cells was evaluated by bright-field microscopy,
intracellular reactive oxygen species (ROS), mitochondrial membrane
potential (MMP), DNA damage, and caspase-3 analyses. The cells treated
with the complexes showed upregulated caspase-3 compared to the control,
and it was found that ROS and MMP were dose-dependent on analysis.
Also, bright-field microscopy and 4′,6-diamidino-2-phenylindole
(DAPI) staining have correspondingly shown cellular membrane
blebbing and DNA damage, which were morphological hallmarks of apoptosis.
The study concluded that the complexes promoted the oxidative stress-mediated
apoptotic death of the cancer cells through the generation of intracellular
ROS, depletion of MMP, and damage of the nuclear material.
Fourteen new RuII–arene (p‐cymene/benzene) complexes (C1–C14) have been synthesized by varying the N‐terminal substituent in the furoylthiourea ligand and satisfactorily characterized by using analytical and spectroscopic techniques. Electrostatic potential maps predicted that the electronic effect of the substituents was mostly localized, with some influence seen on the labile chloride ligands. The structure–activity relationships of the Ru–p‐cymene and Ru–benzene complexes showed opposite trends. All the complexes were found to be highly toxic towards IMR‐32 cancer cells, with C5 (Ru–p‐cymene complex containing C6H2(CH3)3 as N‐terminal substituent) and C13 (Ru–benzene complex containing C6H4(CF3) as N‐terminal substituent) showing the highest activity among each set of complexes, and hence they were chosen for further study. These complexes showed different behavior in aqueous solutions, and were also found to catalytically oxidize glutathione. They also promoted cell death by apoptosis and cell cycle arrest. Furthermore, the complexes showed good binding ability with the receptors Pim‐1 kinase and vascular endothelial growth factor receptor 2, commonly overexpressed in cancer cells.
Six different acylthiourea ligands (L1-L6) and their corresponding Ru(II)-p-cymene complexes (P1-P6) were designed to explore the structure-activity relationship of the complexes under the influence of aliphatic chain length and aromatic...
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