Half-Sandwich Arene Ruthenium(II) Thiosemicarbazone Complexes: Evaluation of Anticancer Effect on Primary and Metastatic Ovarian Cancer Cell Lines.

In this study, we describe the synthesis, characterization and antiproliferative activity of three organo-ruthenium(II) half-sandwich complexes [RuCl(η6-p-cym)(N,S-L)]Cl (I, II, and III). To form these complexes, three thiosemicarbazone ligands (TSCs) were synthesized; L = 5-nitro-2-carboxyaldehyde-thiophen-N-methyl-thiosemicarbazone, (L1); 2-acetyl-5-bromo-thiophen-N-methyl-thiosemicarbazone, (L2) and 2-acetyl-5-bromo-thiophen-N,N-dimethyl-thiosemicarbazone, (L3). The isolated compounds were analyzed using spectroscopic techniques such as elemental analysis, conductance measurements, FT-IR, 1H NMR spectroscopy, MALDI-TOF mass spectrometry, and single-crystal XRD. Our results demonstrated that the synthesized thiosemicarbazone ligands (TSCs) are bound to the metal ion as a bidentate ligand that coordinates through the thiocarbonyl sulfur and azomethine nitrogen atoms in all complexes (I, II, and III). The X-ray crystal structures of L1 and L2 revealed that both compounds are crystallized in the triclinic crystal system with space group P-1. The biological potency of newly synthesized TSC ligands (L1, L2, and L3) and their corresponding ruthenium complexes (I, II, and III) were investigated on human primary ovarian (A2780) and human metastatic ovarian (OVCAR-3) cell lines. To get detailed information respecting antitumor properties, cytotoxicity, DNA/BSA binding affinity, cellular uptake, DNA binding competition, and trans-epithelial resistance measurement assays were performed. Our results demonstrate that newly synthesized ruthenium(II) complexes possess potential biological activity. Moreover, we observe that the ruthenium complexes reported here show anticancer activity on primary (A2780) and metastatic (OVCAR-3) ovarian cancer cells.

Synthesis and characterization of thiosemicarbazone-functionalized organoruthenium (II)-arene complexes: Investigation of antitumor characteristics in colorectal cancer cell lines.

In the current study, organoruthenium(II)-arene complexes (I-IV) have been prepared by the reaction of [{(η6-p-cym)RuCl}2(µ-Cl)2] with new thiosemicarbazones (TSC1-4).The isolate was analyzed using elemental analysis, FT-IR, 1H and 13C NMR spectroscopy and single-crystal XRD. Subsequently, the complexes and TSC ligands were assessed for anticancer properties in vitro against three different colorectal cancer stage's cell lines (Caco-2, DLD-1, and SW620) and a noncancerous cell line (CCD18Co). The complexes (I-IV) showed higher cytotoxicity with low IC50 values as 0.1-0.33 µM in colorectal cell lines except for SW620 (47.4-84.20 µM) than in a noncancerous cell. Complex I was 2.8 and 24.5-fold more active against Caco-2 and DLD-1 than CCD18Co, respectively. The complexes (I-IV) accumulated at a high concentration in the cell nuclei and caused cell cycle arrest by affecting the G0/G1 and/or G2/M phase and showed high binding affinity with CT-DNA (Kb = 104 M-1). The expression of Caspase-3 and Caspase-9 apoptosis-related protein levels was slightly upregulated and Atg5 autophagy-related protein level was clearly downregulated according to control and 5-FU-treated cells after complex I and II treatment. Furthermore, it was observed that cytotoxicity of the complexes is decreased while cancer progresses. Altogether, this study indicates that all organoruthenium (II)-arene complexes (particularly complex I) can be a promising alternative to platinum counterparts in cancer treatment.

Crystal structures, spectroscopic properties of new cobalt(II), nickel(II), zinc(II) and palladium(II) complexes derived from 2-acetyl-5-chloro thiophene thiosemicarbazone: Anticancer evaluation.

The reactions of cobalt(II), nickel(II), zinc(II) chlorides and [Pd(DMSO)2Cl2] with 2-acetyl-5-chloro-thiophene thiosemicarbazone (HL) leads to the formation of a series of new complexes: [CoCl2(S-HL)2], 1; [Ni(N,S-L)2], 2 [ZnCl2(S-HL)2], 3 and [PdCl2(N,S-HL)], 4. All the complexes have been characterized by elemental analysis, IR, LC-MS. 1H and 13C NMR spectroscopy have been performed for Zn(II) and Pd(II) complexes. The crystal structures of the complexes 1-3 have been determined by single-crystal X-ray diffraction methods. The compounds, (1) and (3), crystallized in the monoclinic crystal system with C2/c space group. In both complexes, the metal centers are four-coordinated in a distorted tetrahedral configuration by two sulfur atoms from two thiosemicarbazone ligands and two Cl anions. The crystal structure of (2) consists of monomeric entities where the nickel(II) ion exhibit distorted square planar geometry. The coordination geometry around nickel ion is four-coordinate with four atoms of the two chelating thiosemicarbazone ligands which are in cis position. The τ4 value of 0.255 obtained from the τ4 analysis of complex (2) shows that the four-coordinate geometry around the central nickel ion is close to square planar. Complex (4) is mononuclear, the central ion is coordinated through the sulfur and the azomethine nitrogen atom of neutral ligand. The cytotoxic effects of all complexes were analyzed for three cancer cell lines, Caco-2, DLD-1, and SW620 compared to normal colon epithelial cell line, CCD18Co. Complex (4) is more active against DLD-1, SW620 and Caco-2 than CCD18Co. The efficiency of complex (4) is more effective in aggressive cancer cell lines. Therefore, it can be used as a new chemotherapeutic, especially in the treatment of resistant cancer types caused by long-term use of platinum-based drugs.

Pharmacological prophylaxis of postpartum exacerbation in depressive and anxiety symptoms: a retrospective study.

The aim of this study was to investigate the efficacy of prophylactic treatment with antidepressants for the prevention of postpartum exacerbation in depressive or anxiety symptoms. The study included data on 33 patients who were followed from pregnancy to the postpartum period at the Department of Psychiatry of a university Hospital. Psychiatric diagnoses were determined by means of a structured clinical interview. The severity of depressive and anxiety symptoms were assessed by means of Hamilton Rating Scale for Depression (HAM-D) and Hamilton Rating Scale for Anxiety (HAM-A), respectively. Prophylactic treatment was initiated within the first 3 days after the delivery. The patients were assessed again with HAM-D and HAM-A at 4-week postpartum. Postpartum prophylaxis was carried out with administration of sertraline at 50 mg/day (n = 7, 21.2%), paroxetine at 20 mg/day (n = 24, 72.7%), and escitalopram at 10 mg/day (n = 2, 6.1%). Statistical analyses indicated that the mean HAM-D and HAM-A scores before (9.45 ± 7.01 and 10.09 ± 6.42, respectively) and after (9.09 ± 6.65 and 9.54 ± 5.97, respectively) the delivery were not significant. Results of the present study suggest that prophylactic use of antidepressants following parturition may be useful in the prevention of postpartum exacerbation of symptoms in women with depression or anxiety disorders.

Screening organometallic thiophene containing thiosemicarbazone ruthenium (II/III) complexes as potential anti-tumour agents.

The new ruthenium (III) complex has been synthesized and characterized by elemental analysis, FT-IR, UV-Vis, EI-Mass, EPR spectroscopy, and magnetic susceptibility measurement. Cytotoxic effects of organoruthenium (II/III) complexes 1a, 1b, and 2a, and their ligands (TSC1 and TSC2) in cultured human ovarian (A2780, SKOV-3, and OVCAR-3) and colon (DLD, CCD18Co, and Caco-2) cells have been investigated comparing reactivity of the Ru (II/III) complexes and their free TSC ligands. The complexes exhibit higher cytotoxicity in three cancer cell lines than in normal cells. The binding with CT-DNA and BSA of the all complexes were weak compared with their ligand in spite of the cellular uptake of these complexes into the cytoplasm and then nucleus while their cytotoxic effects were vice versa. All the results showed that Complex 1b has more efficient cytotoxicity on the colon cancer cells than ovarian cancer cells. However, Complex 2a is a better drug candidate especially for antitumor therapy of metastasized ovarian cancer.

Ruthenium (II) complexes of thiosemicarbazone: synthesis, biosensor applications and evaluation as antimicrobial agents.

A conformationally rigid half-sandwich organoruthenium (II) complex [(η(6)-p-cymene)RuClTSC(N-S)]Cl, (1) and carbonyl complex [Ru(CO)Cl(PPh3)2TSC(N-S)] (2) have been synthesized from the reaction of [{(η(6)-p-cymene)RuCl}2(µ-Cl)2] and [Ru(H)(Cl)(CO)(PPh3)3] with thiophene-2-carboxaldehyde thiosemicarbazon (TSC) respectively and both novel ruthenium (II) complexes have been characterized by elemental analysis, FT-IR and NMR spectroscopy. The peripheral TSC in the complexes acts as an electrochemical coupling unit providing the ability to carry out electrochemical deposition (ED) and to form an electro-deposited film on a graphite electrode surface. The biosensing applicability of complexes 1 and 2 was investigated by using glucose oxidase (GOx) as a model enzyme. Electrochemical measurements at -0.9V versus Ag/AgCl electrode by following the ED Ru(II) reduction/oxidation due to from the enzyme activity, in the presence of glucose substrate. The designed biosensor showed a very good linearity for 0.01-0.5mM glucose. The in vitro antimicrobial activities of complexes 1 and 2 were also investigated against nine bacterial strains and one fungus by the disc diffusion test method. No activity was observed against the Gram-negative strains and fungus, whereas complex 1 showed moderate antibacterial activities against Gram-positive bacterial strains.

Combining anti-cancer drugs with artificial sweeteners: synthesis and anti-cancer activity of saccharinate (sac) and thiosaccharinate (tsac) complexes cis-[Pt(sac)2(NH3)2] and cis-[Pt(tsac)2(NH3)2].

The new platinum(II) complexes cis-[Pt(sac)2(NH3)2] (sac=saccharinate) and cis-[Pt(tsac)2(NH3)2] (tsac=thiosaccharinate) have been prepared, the X-ray crystal structure of cis-[Pt(sac)2(NH3)2] x H2O reveals that both saccharinate anions are N-bound in a cis-arrangement being inequivalent in both the solid-state and in solution at room temperature. Preliminary anti-cancer activity has been assessed against A549 human alveolar type-II like cell lines with the thiosaccharinate complex showing good activity.

1,4-Bis[2-(1,3-benzothia-zol-2-yl)phen-oxy]butane.

The mol-ecule of the title compound, C(30)H(24)N(2)O(2)S(2), adopts a transoid conformation consistent with the inversion centre located at the mid-point of the central C-C single bond, resulting in one half mol-ecule in the asymmetric unit. The dihedral angle between the coplanar benzothia-zole ring system and the benzene ring is 11.06 (7)°. In the crystal structure, mol-ecules are linked by weak inter-molecular π-π inter-actions between thia-zole and benzene rings to form a three-dimensional network.