Ru(II)-p-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.

Denticity governs the formation of ß-thioketiminato tri-copper(I) and mono-copper(I) complexes.

Two classes of ß-thioketiminate ligands, SN chelators (HL1 and HL2) and SNN chelators (HL3 and HL4), were prepared to understand their coordination behavior in copper(I) complex formation. The formation of these copper(I) complexes bearing ß-thioketiminate ligands and their corresponding adducts toward isocyanide, PPh3, and CO was investigated to address two important issues. First, whether the denticity governs the copper(I) thiolate species formation between SN chelators and SNN chelators. Second, how the length of the pendant pyridyl arm affects the coordination and reactivity behaviors of copper(I) complexes. Based on the characterization results, it was found that the denticity of SN chelators and SNN chelators led to different nuclearity of copper(I)-thiolate species. The coordination modes of the pendant pyridyl arm were confirmed by FTIR measurements, which allow us to conclude that the electron donating ability of the LCu fragment is in the order of SNN-chelator (SNN bound) > SNN-chelators (SN bound) > SN-chelator.

Bidentate acylthiourea ligand anchored Pd-PPh3 complexes with biomolecular binding, cytotoxic, antioxidant and antihemolytic properties.

Acylthiourea-based Pd(II) complexes (1-5) with a PPh3 moiety bearing the general formula [PdCl(PPh3)(L-R)] [L-R = monoanionic bidentate acylthiourea ligand, where R = C6H5 (L1), C6H4CH3(o) (L2), C6H4OCH2CH3(p) (L3), C10H7 (L4) or C6H4Cl (L5)] have been synthesized and characterized by spectroscopic and analytical tools. The single crystal X-ray structures (1-3) revealed that the acylthiourea ligands coordinated to Pd(II) ion in an uncommon bidentate fashion through S and N atoms, forming a four-member ring. The Pd(II) ion exhibited a square planar geometry fulfilled by the ligand (N, S), one Cl- and one triphenylphosphine (PPh3). Calf thymus (CT) DNA and bovine serum albumin (BSA) binding of the complexes have been analyzed by spectroscopic and molecular docking studies. The complexes were tested for their in vitro cytotoxicity on three cancer (cervical, breast and lung) and one normal (human embryo) cell lines. Complex 4 bearing the naphthalene substitution exhibited the highest activity against three cancer cells with the half-maximal inhibitory concentration (IC50) values of 8.6 (cervical), 8.8 (breast) and 9.4 µM (lung). The acridine orange/ethidium bromide (AO/EB) and 4',6-diamidino-2-phenylindole (DAPI) staining assays indicated that 4 induced cancer cell death through apoptosis. Among the complexes, 4 exhibited the highest 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity of 86.19%. All the complexes were subjected to the hemolysis assay which revealed their biocompatibility with red blood cells (RBCs) with a lysis rate of less than 5 %.

Tris-(2-pyridyl)-pyrazolyl Borate Zinc(II) Complexes: Synthesis, DNA/Protein Binding and In Vitro Cytotoxicity Studies.

Zn(II) complexes bearing tris[3-(2-pyridyl)-pyrazolyl] borate (Tppy) ligand (1-3) was synthesized and examined by spectroscopic and analytical tools. Mononuclear [TppyZnCl] (1) has a Zn(II) centre with one arm (pyrazolyl-pyridyl) dangling outside the coordination sphere which is a novel finding in TppyZn(II) chemistry. In complex [TppyZn(H2O)][BF4] (2) hydrogen bonding interaction of aqua moiety stabilizes the dangling arm. In addition, solution state behaviour of complex 1 confirms the tridentate binding mode and reactivity studies show the exogenous axial substituents used to form the [TppyZnN3] (3). The complexes (1-3) were tested for their ability to bind with Calf thymus (CT) DNA and Bovine serum albumin (BSA) wherein they revealed to exhibit good binding constant values with both the biomolecules in the order of 104-105 M-1. The intercalative binding mode with CT DNA was confirmed from the UV-Visible absorption, viscosity, and ethidium bromide (EB) DNA displacement studies. Further, the complexes were tested for in vitro cytotoxic ability on four triple-negative breast cancer (TNBC) cell lines (MDA-MB-231, MDA-MB-468, HCC1937, and Hs 578T). All three complexes (1-3) exhibited good IC50 values (6.81 to 16.87 µM for 24 h as seen from the MTS assay) results which indicated that these complexes were found to be potential anticancer agents against the TNBC cells.

Binding mode transformation and biological activity on the Ru(II)-DMSO complexes bearing heterocyclic pyrazolyl ligands.

Three Ru(II)-DMSO complexes (1-3) containing 2-(3-pyrazolyl)pyridine (PzPy), 2-pyrazol-3-ylfuran (PzO), or 2-pyrazol-3-ylthiophene (PzS) ligand, were synthesized and characterized. The monodentate coordination of the heterocyclic pyrazolyl ligand (PzPy) with Ru(II) ion via N atom was confirmed by single crystal X-ray diffraction. Complex 1 could be converted to the known η2-bidentate PzPy complex cis(Cl), cis(S)-[RuCl2(PzPy)(DMSO)2] (4) under reflux conditions. The mechanism underlying binding mode transformation was studied by 1H NMR spectroscopy and density functional theory (DFT) calculations. The binding abilities of the complexes (1-4) with calf-thymus (CT) DNA and bovine serum albumin (BSA) were investigated using spectroscopic and molecular docking techniques. Among the four Ru(II) complexes, complexes 1 and 3 inhibited the long-term proliferation of human breast cancer cells, whereas complexes 2 and 4 did not inhibit their proliferation to a considerable extent. Interestingly, complexes 1 and 3 did not induce significant cell death but rather attenuated the clonogenicity of breast cancer cells by upregulating reactive oxygen species (ROS), endoplasmic reticulum (ER) and autophagic stress.