In vitro and in silico assessment of antitumor properties and biomolecular binding studies for two new complexes based on NiII bearing k2N,S-donor ligands.

This work deals with two new molecule-based materials, namely NiII-complexes of general formulae [Ni(L1)2] (Ni1) and [Ni(L2)2] (Ni2), where L1 = trans-cinnamaldehyde-N(4)-methyl thiosemicarbazone and L2 = trans-cinnamaldehyde-N(4)-ethyl thiosemicarbazone, as potential antitumor agents. Both compounds were characterized by elemental analysis, molar conductivity and spectroscopic techniques (FTIR and NMR). Their molecular structures were obtained by single-crystal X-ray diffraction analysis. Each one crystallizes in a monoclinic space group P 21/c, also the asymmetric unit comprises of one NiII ion located on an inversion centre and one anionic ligand, which acts as a κ2N,S-donor affording a five-membered metallaring. The compounds were screened against two selected tumour cell lines (MCF-7 and A549) and non-tumour fibroblasts cell line (MRC-5) via MTT assays. In both tumour cells, all compounds exhibited higher cytotoxicity than the control drug (cisplatin). The IC50 values ranges of 3.70 - 41.37 µM and 1.06 - 14.91 µM were found for MCF-7 and A549, respectively. Importantly, all of them were less toxicity than cisplatin in MRC-5 with SI values ranged at 11.80 - 86.60. The red blood cell (RBC) assay revealed Ni2 as non-toxic due to its reduced haemolytic effect (0--9% at 1--10 µM). The DNA binding was investigated through a combination of spectrophotometric absorption and emission titrations, electrophoresis, and circular dichroism experiments. As a result, these metal complexes were not able to strongly binding to DNA (Kb values ~104 mol L--1) but suggesting groove-binding interactions. The scavenging ability of them towards 2,2-diphenyl-1-picrylhydrazyl (DPPH) free-radical was also evaluated in this work, but no important antioxidant behaviour was detected. Further, the interaction of Ni1 and Ni2 to human serum albumin (HSA) was explored by quenching of tryptophan emission, warfarin competitive assay, and molecular docking protocols. The HSA binding analyses indicated good affinity of both complexes to Sudlow site I (Kb values ⁓103 mol L-1).

Dexamethasone inhibits respiratory syncytial virus-driven mucus production while increasing viral replication without altering antiviral interferon signaling.

Respiratory syncytial virus (RSV) infection can cause mucus overproduction and bronchiolitis in infants leading to severe disease and hospitalization. As a therapeutic strategy, immune modulatory agents may help prevent RSV-driven immune responses that cause severe airway disease. We developed a high throughput screen to identify compounds that reduced RSV-driven mucin 5AC (Muc5AC) expression and identified dexamethasone. Despite leading to a pronounced reduction in RSV-driven Muc5AC, dexamethasone increased RSV infection in vitro and delayed viral clearance in mice. This correlated with reduced expression of a subset of immune response genes and reduced lymphocyte infiltration in vivo. Interestingly, dexamethasone increased RSV infection levels without altering antiviral interferon signaling. In summary, the immunosuppressive activities of dexamethasone had favorable inhibitory effects on RSV-driven mucus production yet prevented immune defense activities that limit RSV infection in vitro and in vivo. These findings offer an explanation for the lack of efficacy of glucocorticoids in RSV-infected patients.

Data of synthesis, characterization and luminescence measurements in 1D lanthanide coordination polymers based on lanthanides.

In this work are presented all the conditions of synthesis explored to obtain a new family of compound with formula [Ln(4-OHBBA)3(H2O)2] (Ln = La, Pr). Powder X ray diffraction was used to identify the different phases obtained in the synthetic study. FT-IR spectroscopy and TG analysis for La and Pr pure phases are also reported. Optical properties of optically active CPs materials, solid state photoluminescence properties of La, Pr, La-(5%Eu) and La-(5%Tb) compounds were explored. We report the absorption, excitation and emission spectrum of the 4'-hydroxi-4-biphenylcarboxylic acid and a comparative description of the radiative (and no-radiative) processes in solid state in Ln-(4-OHBBA) and Ln-BPDC compounds. Finally, a principal component analysis was conducted in order to take in account both signal contributions from the sensor (LCE at 384 nm and the europium emission at 610 nm) and for classifying the type of analytes used to test the sensing response of the materials.

'There was just no-one there to acknowledge that it happened to me as well': A qualitative study of male partner's experience of miscarriage.

Miscarriage occurs in up to one in four pregnancies and can be a devastating event affecting both men and women. Unfortunately, the male partner's experience of miscarriage is seldom researched, particularly within Australia. This qualitative study involved semi-structured telephone interviews with 10 Australian men, whose partners miscarried between three months and ten years ago. Participants were recruited through professional networks and support organisations. Interviews explored men's general miscarriage experience and the support received or lacking from both healthcare providers and social networks. Online health seeking behaviour and opinions on online support were also discussed. Data was transcribed verbatim and analysed thematically. Most men described feeling significant grief following miscarriage and felt that there was little acknowledgment of their loss, both from healthcare providers and within their social networks. Feelings of sadness, devastation, powerlessness, fear, shock and a loss of identity were common. All men felt their primary role at the time of miscarriage was to support their partner. Most men did not want to burden their partner with their emotions or grief, and struggled to find people within their social networks to talk to about their loss, leading to feelings of isolation. Overall participants felt there was inadequate support offered to men affected by miscarriage. Men wanted information, informed professionals to talk to and male-orientated support networks. A website was one mechanism suggested by men which could adequately contribute to information and support needs during this time. Men are often greatly affected by miscarriage and yet there is all too often little acknowledgement or support available to them at this time. Men affected by miscarriage want and need further support, including reputable, Australian based information and resources tailored their needs.

Exploring physical and chemical properties in new multifunctional indium-, bismuth-, and zinc-based 1D and 2D coordination polymers.

Main group element coordination polymers (MGE-CPs) are important compounds for the development of multifunctional materials. However, there has been a shortage of studies regarding their structural, optical, catalytic, mechanical, and antibacterial properties. This work presents an exhaustive study of a set of crystalline MGE-CPs obtained from bismuth and indium metals and iminodiacetate, 1,2,4,5-benzenetetracarboxylate, and 2,2'-bipyridine as building blocks. An in-depth topological analysis of the networks was carried out. Additionally, nanoindentation studies were performed on two representative low-dimensional compounds in order to find the relationships between their structural features and their intrinsic mechanical properties (hardness and elasticity). The solid-state photoluminescence (SSPL) properties were also studied in terms of excitation, emission, lifetimes values, and CIE chromaticites. Moreover, the heterogeneous catalytic activities of the compounds were evaluated with the cyanosilylation reaction using a set of carbonylic substrates under solvent-free conditions. Finally, the inhibitory effect of the Bi-CPs on the growth of microorganisms such as Escherichia coli, Salmonella enterica serovar Typhimurium, and Pseudomonas aeruginosa, which are associated with relevant infectious diseases, is reported.

Pseudopolymorphism in hydroxybenzophenones: the dihydrate of 2,2',4,4'-tetrahydroxybenzophenone.

A dihydrate pseudopolymorph of bis(2,4-dihydroxyphenyl)methanone, C(13)H(10)O(5)·2H(2)O, (I), was obtained during polymorphism screening of hydroxybenzophenone derivatives. This structure, in which the molecule sits on a twofold axis, was compared with the known anhydrous form of (I) [Schlemper (1982). Acta Cryst. B38, 554-559]. The role of water in the crystal assembly was established on the basis of the known monohydrate pseudopolymorph of 3,4-dihydroxybenzophenone [Landre, Souza, Corrêa, Martins & Doriguetto (2010). Acta Cryst. C66, o463-o465].

Pleiotropic effects of statins in distal human pulmonary artery smooth muscle cells.

BACKGROUND: Recent clinical data suggest statins have transient but significant effects in patients with pulmonary arterial hypertension. In this study we explored the molecular effects of statins on distal human pulmonary artery smooth muscle cells (PASMCs) and their relevance to proliferation and apoptosis in pulmonary arterial hypertension. METHODS: Primary distal human PASMCs from patients and controls were treated with lipophilic (simvastatin, atorvastatin, mevastatin and fluvastatin), lipophobic (pravastatin) and nitric-oxide releasing statins and studied in terms of their DNA synthesis, proliferation, apoptosis, matrix metalloproteinase-9 and endothelin-1 release. RESULTS: Treatment of human PASMCs with selected statins inhibited DNA synthesis, proliferation and matrix metalloproteinase-9 production in a concentration-dependent manner. Statins differed in their effectiveness, the rank order of anti-mitogenic potency being simvastatin > atorvastatin > > pravastatin. Nevertheless, a novel nitric oxide-releasing derivative of pravastatin (NCX 6550) was effective. Lipophilic statins, such as simvastatin, also enhanced the anti-proliferative effects of iloprost and sildenafil, promoted apoptosis and inhibited the release of the mitogen and survival factor endothelin-1. These effects were reversed by mevalonate and the isoprenoid intermediate geranylgeranylpyrophosphate and were mimicked by inhibitors of the Rho and Rho-kinase. CONCLUSIONS: Lipophilic statins exert direct effects on distal human PASMCs and are likely to involve inhibition of Rho GTPase signalling. These findings compliment some of the recently documented effects in patients with pulmonary arterial hypertension.

Redetermination of 1-benzyl-3-furoyl-1-phenyl-thio-urea.

The title compound, C(19)H(16)N(2)O(2)S, was synthesized from furoyl isothio-cyanate and N-benzyl-aniline in dry acetone and the structure redetermined. The structure [Otazo-Sánchez et al. (2001 ▶). J. Chem. Soc. Perkin Trans. 2, pp. 2211-2218] has been re-determined in order to establish the intramolecular and intermolecular inter-actions. The thio-urea group is in the thio-amide form. The thio-urea group makes a dihedral angle of 29.2 (6)° with the furoyl group. In the crystal structure, mol-ecules are linked by inter-molecular C-H⋯O inter-actions, forming one-dimensional chains along the a axis. An intra-molecular N-H⋯O hydrogen bond is also present.

1-Furoyl-3-[3-(trifluoro-meth-yl)phen-yl]thio-urea.

The title compound, C(13)H(9)F(3)N(2)O(2)S, crystallizes with two independent mol-ecules in the asymmetric unit. The central thio-urea core is roughly coplanar with the furan and benzene rings, showing O-C-N-C(S) torsion angles of 2.3 (4) and -11.4 (2)° and (S)C-N-C-C torsion angles of -2.4 (4) and -28.8 (4)°, respectively, in the two independent mol-ecules. The trans-cis geometry of the thio-urea fragment is stabilized by an intra-molecular N-H⋯O hydrogen bond between the H atom of the cis thio-amide and the carbonyl O atom. In the crystal structure, inter-molecular N-H⋯S hydrogen bonds form centrosymmetric dimers extending along the b axis.

8-Hydr-oxy-5,6,7-trimeth-oxy-2-phenyl-4H-chromen-4-one.

In the title compound, C(18)H(16)O(6), the benzopyran group is essentially planar, with the O atoms of the substituent groups lying close to its mean plane. The mol-ecular conformation is governed by intra-molecular inter-actions. The crystal packing is mainly determined by one classical inter-molecular hydrogen bond which gives rise to the formation of an infinite chain along the a axis.

1-Furfuryl-3-furoylthio-urea.

The title compound, C(11)H(10)N(2)O(3)S, was synthesized from furoyl isothio-cyanate and furfurylamine in dry acetone. The thio-urea group is in the thio-amide form. The trans-cis geometry of the thio-urea group is stabilized by intra-molecular hydrogen bonding between the carbonyl and cis-thio-amide and results in a pseudo-S(6) planar ring which makes dihedral angles of 2.5 (3) and 88.1 (2)° with the furoyl and furfuryl groups, respectively. There is also an intra-molecular hydrogen bond between the furan O atom and the other thio-amide H atom. In the crystal structure, mol-ecules are linked by two inter-molecular N-H⋯O hydrogen bonds, forming dimers. These dimers are stacked within the crystal structure along the [010] direction.

1-(2-Furo-yl)-3-(o-tol-yl)thio-urea.

The title compound, C(13)H(12)N(2)O(2)S, was synthesized from furoyl isothio-cyanate and o-toluidine in dry acetone. The thio-urea group is in the thio-amide form. The central thio-urea fragment makes dihedral angles of 2.6 (1) and 22.4 (1)° with the ketofuran group and the benzene ring, respectively. The mol-ecular structure is stabilized by N-H⋯O hydrogen bonds. In the crystal structure, centrosymmetrically related mol-ecules are linked by a pair of N-H⋯S hydrogen bonds to form a dimer with an R(2) (2)(6) ring motif.

N-(2-Furylcarbon-yl)piperidine-1-carbo-thio-amide.

The title compound, C(11)H(14)N(2)O(2)S, was synthesized from furoyl isothio-cyanate and piperidine in dry acetone. The thio-urea group is in the thio-amide form. The thio-urea group makes a dihedral angle of 53.9 (1)° with the furan carbonyl group. In the crystal structure, mol-ecules are linked by inter-molecular N-H⋯O hydrogen bonds, forming one-dimensional chains along the c axis. An intramolecular N-H⋯O hydrogen bond is also present.

Synthesis and characterization of a new mebendazole salt: mebendazole hydrochloride.

Mebendazole hydrochloride [(5-benzoyl-1H-benzimidazole-2-yl)-carbamic acid methyl ester hydrochloride, MBZ.HCl], a new stable salt of mebendazole (MBZ), has been synthesized and characterized. It can easily be obtained from recrystallization of forms A, B, or C of MBZ in diverse solvents with the addition of hydrochloric acid solution. Crystallographic data reveals that the particular conformation adopted by the carbamic group contributes to the stability of the network. The crystal packing is stabilized by the presence of three N-H...Cl intermolecular interactions that form chains along the b axis. The XRD analyses of the three crystalline habits found in the crystallization process (square-based pyramids, pseudohexagonal plates, and prismatic) show equivalent diffraction patterns. The vibrational behavior is consistent with crystal structure. The most important functional groups show shifts to lower or higher frequencies in relation to the MBZ polymorphs. The thermal study on MBZ.HCl indicates that the compound is stable up to 160 degrees C approximately. Decomposition occurs in four steps. In the first step the HCl group is eliminated, and after that the remaining MBZ polymorph A decomposes in three steps, as happens with polymorphs B and C. (

Low-temperature study of a new nevirapine pseudopolymorph.

THE TITLE COMPOUND (SYSTEMATIC NAME: 11-cyclo-propyl-4-methyl-5,11-dihydro-6H-dipyrido[3,2-b:2',3'-e][1,4]diazepin-6-one butanol 0.3-solvate), C(15)H(14)N(4)O·0.3C(4)H(9)OH, was crystallized in a new triclinic pseudopolymorphic form, a butanol solvate, and the crystal structure determined at 150 K. The mol-ecular conformation of this new form differs from that reported previously, although the main inter-molecular hydrogen-bond pattern remains the same. N-H⋯O hydrogen bonds [N⋯O = 2.957 (3) Å] form centrosymmetric dimers and the crystal packing of this new pseudopolymorph generates infinite channels along the b axis.

A duplicated nitrotienyl derivative with antimycobacterial activity: synthesis, X-ray crystallography, biological and mutagenic activity tests.

A duplicated nitrotienyl derivative was obtained as a by-product from the synthesis of a proposed molecular hybrid of a nitrotienyl derivative and isoniazid with an expected dual antimycobacteria mechanism. The structure was shown to be the 5,5'-dinitro-2-(2,3-diaza-4-(2'-tienyl)buta-1,3-dienyl)tiophene by X-ray crystallography. The minimal inhibitory concentration (MIC) determination of this compound proved to be promising against Mycobacterium pathogenic strains such as M. avium and M. kansasii, although it had a high level of mutagenicity, as observed in mutagenic activity tests.

Copper complexes with heterocyclic sulfonamides: synthesis, spectroscopic characterization, microbiological and SOD-like activities: crystal structure of [Cu(sulfisoxazole)2(H2O)4] . 2H2O.

The synthesis, characterization and comparative biological study of a series of antibacterial copper complexes with heterocyclic sulfonamides were reported. Two kinds of complexes were obtained with the stoichiometries [Cu(L)2] . H2O and [Cu(L)2(H2O)4] . nH2O. They were characterized by infrared and electronic spectroscopies and the crystal structure of [Cu(sulfisoxazole)2(H2O)4] . 2H2O was determined by single crystal X-ray diffraction. It crystallized in the C2/c with Z = 8 monoclinic space group C2/c with Z = 8. The Cu(II) is in a slightly tetragonal distorted octahedron formed by four oxygen atoms from water molecules and two nitrogen atoms from two isoxazole rings. The antimicrobial activity was evaluated for all the synthesized complexes and ligands using the agar dilution test. The results showed that the complexes with five-membered heterocyclic rings were more active than the free sulfonamides while the pyrimidine, pyridine and pyridazine complexes had similar or less activity than the free ligands. In order to find an explanation for this behavior lipophilicity and superoxide dismutase-like activity were tested, showing that the [Cu(sulfamethoxazol)2(H2O)4] . 3H2O presented the highest antimicrobial potency and a superoxide dismutase-like activity comparable with pharmacological active compounds.

Phosphodiesterase type 4 expression and anti-proliferative effects in human pulmonary artery smooth muscle cells.

BACKGROUND: Pulmonary arterial hypertension is a proliferative vascular disease, characterized by aberrant regulation of smooth muscle cell proliferation and apoptosis in distal pulmonary arteries. Prostacyclin (PGI2) analogues have anti-proliferative effects on distal human pulmonary artery smooth muscle cells (PASMCs), which are dependent on intracellular cAMP stimulation. We therefore sought to investigate the involvement of the main cAMP-specific enzymes, phosphodiesterase type 4 (PDE4), responsible for cAMP hydrolysis. METHODS: Distal human PASMCs were derived from pulmonary arteries by explant culture (n = 14, passage 3-12). Responses to platelet-derived growth factor-BB (5-10 ng/ml), serum, PGI2 analogues (cicaprost, iloprost) and PDE4 inhibitors (roflumilast, rolipram, cilomilast) were determined by measuring cAMP phosphodiesterase activity, intracellular cAMP levels, DNA synthesis, apoptosis (as measured by DNA fragmentation and nuclear condensation) and matrix metalloproteinase-2 and -9 (MMP-2, MMP-9) production. RESULTS: Expression of all four PDE4A-D genes was detected in PASMC isolates. PDE4 contributed to the main proportion (35.9 +/- 2.3%, n = 5) of cAMP-specific hydrolytic activity demonstrated in PASMCs, compared to PDE3 (21.5 +/- 2.5%), PDE2 (15.8 +/- 3.4%) or PDE1 activity (14.5 +/- 4.2%). Intracellular cAMP levels were increased by PGI2 analogues and further elevated in cells co-treated with roflumilast, rolipram and cilomilast. DNA synthesis was attenuated by 1 microM roflumilast (49 +/- 6% inhibition), rolipram (37 +/- 6%) and cilomilast (30 +/- 4%) and, in the presence of 5 nM cicaprost, these compounds exhibited EC50 values of 4.4 (2.6-6.1) nM (Mean and 95% confidence interval), 59 (36-83) nM and 97 (66-130) nM respectively. Roflumilast attenuated cell proliferation and gelatinase (MMP-2 and MMP-9) production and promoted the anti-proliferative effects of PGI2 analogues. The cAMP activators iloprost and forskolin also induced apoptosis, whereas roflumilast had no significant effect. CONCLUSION: PDE4 enzymes are expressed in distal human PASMCs and the effects of cAMP-stimulating agents on DNA synthesis, proliferation and MMP production is dependent, at least in part, on PDE4 activity. PDE4 inhibition may provide greater control of cAMP-mediated anti-proliferative effects in human PASMCs and therefore could prove useful as an additional therapy for pulmonary arterial hypertension.

The synthesis and characterisation of Sn(IV) complexes of 2,6-pyridine dicarboxylate--the molecular structure of divinyltin(IV) derivative.

A series of organotin(IV) derivatives were obtained employing 2,6-pyridinedicarboxylate as ligand: [{SnBu3(OOC)2C5H3N}n] (1), [SnBuCl(OOC)2C5H3N] (2) and [Sn(CHCH2)2(OOC)2C5H3N] (3). They were fully characterised by multinuclear NMR [1H, 13C{1H}, and 119Sn{1H}], IR spectroscopies and elemental analysis. In addition suitable crystals of (3) have shown a dimmeric arrangement by X-ray crystallographic studies, held together by Sn-O intermolecular interactions which persists in solution. The crystal packing shows hydrogen bonds joining the dimmers, forming two infinite one-dimensional chain. Each monomer comprises a Sn(IV) centre bonded to a pyridinecarboxylate-containing ring, through both nitrogen and oxygen donor atoms. It is also co-ordinated by a water molecule and two vinyl groups.