Base-Catalyzed Reaction of Isatins and (3-Hydroxyprop-1-yn-1-yl)phosphonates as a Tool for the Synthesis of Spiro-1,3-dioxolane Oxindoles with Anticancer and Anti-Platelet Properties.

An approach to the synthesis of phosphoryl substituted spiro-1,3-dioxolane oxindoles was developed from the base-catalyzed reaction of various isatins with (3-hydroxyprop-1-yn-1-yl)phosphonates. It was found that various aryl-substituted and N-functionalized isatins with the formation of appropriate products with high yields and stereoselectivity when using -BuOLi are able to react. Cytotoxic activity evaluation suggests that the most significant results in relation to the HuTu 80 cell line were shown by N-benzylated spirodioxolanes.

Antioxidative and cardioprotective effects of minocycline in ischemia/reperfusion injury in experimental model of hypertension.

Cardiovascular diseases remains leading cause of death and disabilities. Coronary artery occlusion and consequent ischemia leads to acute myocardial infarction, but restoration of blood flow, paradoxically, provokes further myocardial damage known as reperfusion injury. Minocycline is possessing anti-inflammatory and anti-apoptotic activity, immune-modulating and antioxidative properties besides its primary antibacterial effect.

The Development of a Method for Obtaining (L.) Sch. Bip. Herb Extract Enriched with Flavonoids and an Evaluation of Its Biological Activity.

The development of new drugs derived from plant sources is of significant interest in modern pharmacy. One of the promising plant sources for introduction into pharmaceuticals is (L.) Sch.

Sn and Ge Complexes with Redox-Active Ligands as Efficient Interfacial Membrane-like Buffer Layers for p-i-n Perovskite Solar Cells.

Inverted perovskite solar cells with a p-i-n configuration have attracted considerable attention from the research community because of their simple design, insignificant hysteresis, improved operational stability, and low-temperature fabrication technology. However, this type of device is still lagging behind the classical n-i-p perovskite solar cells in terms of its power conversion efficiency. The performance of p-i-n perovskite solar cells can be increased using appropriate charge transport and buffer interlayers inserted between the main electron transport layer and top metal electrode.

Supramolecular D⋯A-layered structures based on germanium complexes with 2,3-dihydroxynaphthalene and ,'-bidentate ligands.

The concept of using redox-active ligands, which has become extremely widespread in organometallic chemistry, is often considered from 'their effect on the metal center properties' point of view and 'how to modify the ligands'. In this paper, we present the reverse side of this effective approach - a dramatic change of redox properties of ligands under the influence of a redox-inert metal. Germanium derivatives based on 2,3-dihydroxynaphthalene (1) and ,'-bidentate ligands, namely 2,2'-bipyridine (2) and 1,10-phenanthroline (3), were obtained and characterized by CV, UV-vis spectroscopy, DFT calculations and in the case of 3 X-ray diffraction.

Therapeutic Effect of Novel Cyanopyrrolidine-Based Prolyl Oligopeptidase Inhibitors in Rat Models of Amnesia.

Prolyl oligopeptidase (POP) is a large cytosolic serine peptidase that is altered in patients with Alzheimer's disease, Parkinsonian syndrome, muscular dystrophies, and other denervating diseases. Thus, POP may represent a relevant therapeutic target for treatment of neuropsychiatric disorders and neurodegenerative diseases. Here, we report the characterization of five novel cyanopyrrolidine-based compounds (BocTrpPrdN, BocGlyPrdN, CbzMetPrdN, CbzGlnPrdN, and CbzAlaPrdN) and show that they are potent inhibitors of POP and are predicted to penetrate the blood-brain barrier (BBB).

Uridine treatment prevents myocardial injury in rat models of acute ischemia and ischemia/reperfusion by activating the mitochondrial ATP-dependent potassium channel.

The effect of uridine on the myocardial ischemic and reperfusion injury was investigated. A possible mechanism of its cardioprotective action was established. Two rat models were used: (1) acute myocardial ischemia induced by occlusion of the left coronary artery for 60 min; and (2) myocardial ischemia/reperfusion with 30-min ischemia and 120-min reperfusion.

Effects of glucagon-like peptide 1 analogs in combination with insulin on myocardial infarct size in rats with type 2 diabetes mellitus.

Aim: To evaluate the effects of glucagon-like peptide-1 analogs (GLP-1a) combined with insulin on myocardial ischemia-reperfusion injury in diabetic rats.

Methods: Type 2 diabetes mellitus (T2DM) was induced in male Wistar rats with streptozotocin (65 mg/kg) and verified using an oral glucose tolerance test. After anesthesia, the left coronary artery was occluded for 40 min followed by 80 min reperfusion.

The regulatory interplay between Oct-1 isoforms contributes to hematopoiesis and the isoforms imbalance correlates with a malignant transformation of B cells.

Oct-1(POU2F1) is a DNA-binding transcription regulator and its level being highly increased in many human cancers. Oct-1 is present in the human cells as a family of functionally different isoforms which are transcribed from alternative promoters. Here, we have demonstrated that expression patterns of Oct-1 isoforms change during differentiation of hematopoetic progenitor cells (CD34+) (HPCs) to the B (CD19+) and T (CD3+) cells.

Chronic TCDD exposure results in the dysregulation of gene expression in splenic B-lymphocytes and in the impairments in T-cell and B-cell differentiation in mouse model.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) exposure in humans is associated with marked immune suppressions and increased incidence of lymphoblastic diseases. To elucidate mechanisms of impairments in humoral immune responses, we used a murine model. Following a 20-week administration of low doses of TCDD, we observed severely reduced antibody titers, dramatically decreased number of splenic Th1 and Th2 cells and an increase in CD19(+) B cells.

A versatile, bar-coded nuclear marker/reporter for live cell fluorescent and multiplexed high content imaging.

The screening of large numbers of compounds or siRNAs is a mainstay of both academic and pharmaceutical research. Most screens test those interventions against a single biochemical or cellular output whereas recording multiple complementary outputs may be more biologically relevant. High throughput, multi-channel fluorescence microscopy permits multiple outputs to be quantified in specific cellular subcompartments.

Allosteric peptides bind a caspase zymogen and mediate caspase tetramerization.

The caspases are a family of cytosolic proteases with essential roles in inflammation and apoptosis. Drug discovery efforts have focused on developing molecules directed against the active sites of caspases, but this approach has proved challenging and has not yielded any approved therapeutics. Here we describe a new strategy for generating inhibitors of caspase-6, a potential therapeutic target in neurodegenerative disorders, by screening against its zymogen form.

Unusual isotope effect in the reaction of chlorosilylene with trimethylsilane-1-d. Absolute rate studies and quantum chemical and Rice-Ramsperger-Kassel-Marcus calculations provide strong evidence for the involvement of an intermediate complex.

Time-resolved studies of chlorosilylene, ClSiH, generated by the 193 nm laser flash photolysis of 1-chloro-1-silacyclopent-3-ene, have been carried out to obtain rate constants for its bimolecular reaction with trimethylsilane-1-d, Me(3)SiD, in the gas phase. The reaction was studied at total pressures up to 100 Torr (with and without added SF(6)) over the temperature range of 295-407 K. The rate constants were found to be pressure independent and gave the following Arrhenius equation: log[(k/(cm(3) molecule(-1) s(-1))] = (-13.

Gas-phase kinetics of chlorosilylene reactions II. ClSiH + C2H4: absolute rate measurements and quantum chemical and RRKM calculations for the prototype pi addition reaction.

Time-resolved studies of chlorosilylene, ClSiH, generated by the 193 nm laser flash photolysis of 1-chloro-1-silacyclopent-3-ene, are carried out to obtain rate constants for its bimolecular reaction with ethene, C(2)H(4), in the gas-phase. The reaction is studied over the pressure range 0.13-13.

Scalable total synthesis and biological evaluation of haouamine A and its atropisomer.

A total synthesis of the complex, bent aromatic ring-containing marine alkaloid haouamine A is achieved through a route in which every step (with the exception of the final deprotection) is performed on a gram-scale. This is accomplished through the development of a method for the dehydrogenation of cyclohexenones that allows for point-to-planar chirality transfer. This strategy makes it possible to program the desired atropisomeric outcome from a simple chiral cyclohexenone.

Gas-phase kinetics of chlorosilylene reactions. I. ClSiH + Me3SiH: absolute rate measurements and theoretical calculations for prototype Si-H insertion reactions.

Time-resolved studies of chlorosilylene, ClSiH, generated by the 193 nm laser flash photolysis of 1-chloro-1-silacyclopent-3-ene, have been carried out to obtain rate constants for its bimolecular reaction with trimethylsilane, Me(3)SiH, in the gas phase. The reaction was studied at total pressures up to 100 torr (with and without added SF(6)) over the temperature range 297-407 K. The rate constants were found to be pressure independent and gave the following Arrhenius equation: log(k/cm(3) molecule(-1) s(-1)) = (-13.

The structure of corepressor Dax-1 bound to its target nuclear receptor LRH-1.

The Dax-1 protein is an enigmatic nuclear receptor that lacks an expected DNA binding domain, yet functions as a potent corepressor of nuclear receptors. Here we report the structure of Dax-1 bound to one of its targets, liver receptor homolog 1 (LRH-1). Unexpectedly, Dax-1 binds to LRH-1 using a new module, a repressor helix built from a family conserved sequence motif, PCFXXLP.

Structure of SF-1 bound by different phospholipids: evidence for regulatory ligands.

Despite the fact that many nuclear receptors are ligand dependent, the existence of obligate regulatory ligands is debated for some receptors, including steroidogenic factor 1 (SF-1). Although fortuitously bound bacterial phospholipids were discovered in the structures of the SF-1 ligand-binding domain (LBD), these lipids might serve merely as structural ligands. Thus, we examined whether exogenously added phospholipids would exchange for these bacterial lipids and bind to SF-1.

Surprisingly slow reaction of dimethylsilylene with dimethylgermane: time-resolved kinetic studies and related quantum chemical calculations.

Time-resolved studies of silylene, SiH2, and dimethylsilylene, SiMe2, generated by the 193 nm laser flash photolysis of appropriate precursor molecules have been carried out to obtain rate constants for their bimolecular reactions with dimethylgermane, Me2GeH2, in the gas phase. SiMe2 + Me2GeH2 was studied at five temperatures in the range 299-555 K. Problems of substrate UV absorption at 193 nm at temperatures above 400 K meant that only three temperatures could be used reliably for rate constant measurement.

A comparison of the reactivity of germylene and dimethylgermylene with some methylgermanes. Direct kinetic and quantum chemical studies.

Time-resolved studies of germylene, GeH(2), and dimethygermylene, GeMe(2), generated by the 193 nm laser flash photolysis of appropriate precursor molecules have been carried out to try to obtain rate coefficients for their bimolecular reactions with dimethylgermane, Me(2)GeH(2), in the gas-phase. GeH(2) + Me(2)GeH(2) was studied over the pressure range 1-100 Torr with SF(6) as bath gas and at five temperatures in the range 296-553 K. Only slight pressure dependences were found (at 386, 447 and 553 K).

C-reactive protein: a pentraxin with anti-acetylcholine activity.

Purified C-reactive protein (CRP) diminished effects of acetylcholine (ACh) on the vascular tone and the heart rate of rats in vivo. In vitro CRP inhibited breakdown of ACh by acetylcholinesterase (AChE) while did not interact with AChE itself. CRP appears to bind ACh.

Direct time-resolved study of the gas-phase reactions of germylene with ethyl- and diethylgermane: absolute rate constants, temperature dependences, and mechanism.

Time-resolved studies of germylene, GeH2, generated by the 193 nm laser flash photolysis of 3,4-dimethyl-1-germacyclopent-3-ene, have been carried out to obtain rate constants for its bimolecular reactions with ethyl- and diethylgermanes in the gas phase. The reactions were studied over the pressure range 1-100 Torr with SF6 as bath gas and at five temperatures in the range 297-564 K. Only slight pressure dependences were found for GeH2 + EtGeH3 (399, 486, and 564 K).