In this study, half-sandwich Ru(II) complexes containing acylthiourea ligands of the general type [Ru(η 6 -p-cymene)(PPh 3 )-(S)Cl]PF 6 (1m−6m) and [Ru(η 6 -p-cymene)(PPh 3 )(S−O)]PF 6 (1b− 6b) where S/S−O = N',N'-disubstituted acylthiourea were synthesized and characterized (via elemental analyses, IR spectroscopy, 1 H NMR spectroscopy, 13 C{ 1 H} NMR spectroscopy, and X-ray diffractometry), and their cytotoxic activity was evaluated. The different coordination modes of the acylthiourea ligands, monodentately via S (1m−6m) and bidentately via S,O (1b−6b), to ruthenium were modulated from different synthetic routes. The cytotoxicity of the complexes was evaluated in five human cell lines (DU-145, A549, MDA-MB-231, MRC-5, and MCF-10A) by MTT assay. The IC 50 values for prostate cancer cells (2.89−7.47 μM) indicated that the complexes inhibited cell growth, but that they were less cytotoxic than cisplatin (2.00 μM). Unlike for breast cancer cells (IC 50 = 0.28−0.74 μM) and lung cancer cells (IC 50 = 0.51−1.83 μM), the complexes were notably more active than the reference drug, and a remarkable selectivity index ) was observed for breast cancer cells. Based on both the activity and selectivity, complexes 5b and 6b, as well as their respective analogous complexes in the monodentate coordination 5m and 6m, were chosen for further investigation in the MDA-MB-231 cell line. These complexes not only induced morphology changes but also were able to inhibit colony formation and migration. In addition, the complexes promoted cell cycle arrest at the sub-G 1 phase inducing apoptosis. Interaction studies by viscosity measurements, gel electrophoresis, and fluorescence spectroscopy indicated that the complexes interact with the DNA minor groove and exhibit an HSA binding affinity.
1-Acyl thioureas [RC(O)NHC(S)NRR] are shown to display conformational flexibility depending on the degree of substitution at the nitrogen atom. The conformational landscape and structural features for two closely related thioureas having R=2-furoyl have been studied. The un-substituted 2-furoyl thiourea (I) and its dimethyl analogue, i.e. 1-(2-furoyl)-3,3-dimethyl thiourea (II), have been synthesized and fully characterized by spectroscopic (FT-IR, H andC NMR) and elemental analysis. According to single crystal X-ray diffraction analysis, compounds I and II crystallize in the monoclinic space group P21/c. In the compound I, the trans-cis geometry of the almost planar thiourea unit is stabilized by intramolecular NH⋯OC hydrogen bond between the H atom of the cis thioamide and the carbonyl O atom. In compound II, however, the acyl thiourea group is non-planar, in good agreement with the potential energy curve computed at the B3LYP/6-31+G(d,p) level of approximation. Centrosymmetric dimers generated by intermolecular NH⋯SC hydrogen bond forming R(8) motif are present in the crystals. Intermolecular interactions have been rationalized in terms of topological partitions of the electron distributions and Hirshfeld surface analysis, which showed the occurrence of S⋯H, O⋯H and H⋯H contacts that display an important role to crystal packing stabilization of both thiourea derivatives.
Herein we report the synthesis and characterization of a new copper(I) complex with triphenylphosphine (PPh 3 ) and N-(2thiophenecarbonyl)-N'-(3-Cl, 4-F-phenyl)thiourea (HL), as ligands. The complex was characterized by vibrational (FTIR and FT-Raman) and multinuclear ( 1 H, 13 C { 1 H}, 31 P{ 1 H}) NMR spectroscopies. The crystalline structure of the complex was determined by single-crystal X-ray diffraction, confirming that a neutral binuclear compound, identified as [Cu(PPh 3 )(L-k 2 -N,μ-S)] 2 , was obtained. The anionic thiourea ligand coordinates to the metal through the sulfur and nitrogen atoms in an unusual bidentate k 2 -N,μ-S coordination mode. The complex is a dimer sited on a crystallographic center of symmetry. Each Cu 2 (μ-S) 2 cation bridges trough the sulfur atoms of two symmetry related thiourea moieties and is also coordinated to the nitrogen atom of the thiourea ligand and the phosphorus atom from PPh 3 coligand, forming a slightly distorted tetrahedral geometry. An intramolecular NÀ H⋅⋅⋅O=C hydrogen bond is observed in the anionic ligand, forming a six-membered ring that stabilizes the NÀ H thioamide group. Hirshfeld surface analysis shows that the molecules are connected by weak intermolecular contacts C⋅⋅⋅C, H⋅⋅⋅C and H⋅⋅⋅H which add to the stability of the crystalline packing. The in vitro cytotoxicity study of the complex indicates that it is more active against human lung carcinoma cells (A549), when compared to the free ligand.
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