Synthesis and Anticancer Activity of [RuCl₂(η⁶-arene)(aroylthiourea)] Complexes—High Activity against the Human Neuroblastoma (IMR-32) Cancer Cell Line

Abstract

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.

Tunable Anticancer Activity of Furoylthiourea‐Based RuII–Arene Complexes and Their Mechanism of Action

“…The Ru II –arene complexes were synthesized by adding the [Ru(arene)Cl 2 ] 2 (arene= p ‐cymene or benzene) precursor to a solution of the corresponding ligand in toluene (Scheme 2). A few drops of methanol were added to promote the solubility of the metal precursor [19] . The reaction was allowed to proceed for 4 h, after which the ligand spot in TLC had completely disappeared.…”

“…More recently, we have diverted our efforts towards aroylthiourea‐based Ru II –arene complexes, which have resulted in potential anticancer agents (Figure 3). [17–19] …”

Synthesis of Palladium(II) Complexes via Michael Addition: Antiproliferative Effects through ROS-Mediated Mitochondrial Apoptosis and Docking with SARS-CoV-2

“…The apoptotic features such as nuclear swelling, cytoplasmic vacuolation, chromatin fragmentation, and cytoplasmic blebbing were observed. 3 Figuratively, the viable cells (control) contained green nuclei alongside an ordered structure, and early apoptotic cells contained green nuclei besides perinuclear chromatin condensation as bright green patches. Late apoptotic cells contained orange to red nuclei alongside condensed chromatin, and necrotic cells of homogeneously larger size contained orange to red nuclei without condensed chromatin.…”

“…The capability of complex 3 to display higher cytotoxicity than the other two complexes may be attributed to its ability to effectively generate ROS which promote apoptosis. 3 , 95 …”

“…However, their dosage is restrained due to their unsympathetic side effects such as nausea, vomiting, loss of sensation in the extremities, and nephrotoxicity. 3 , 4 Pd(II) complexes are noteworthy alternatives for the treatment of cancer because of their structural and thermodynamic similarities to Pt(II) complexes. 5 − 7 There have been numerous reports on Pd(II) complexes with potential anticancer properties against various cancer cell lines (lung, prostate, etc.…”