Synthesis and Biological Evaluation of Novel Thymidine Analogs Containing 1-1,2,3-Triazolyl, 1-Tetrazolyl, and 2-Tetrazolyl Fragments.

3'-Azidothymidine (AZT) reacts with 1-propargyl-5-R-1- and 2-propargyl-5-R-2-tetrazoles (R = H, Me, CHCOOEt, CHCON(CH), Ph, 2-CH-CH, or 4-NO-CH) the Cu(I)-catalyzed asymmetric [3 + 2] cycloaddition to give 3'-modified thymidine analogs incorporating 1-1,2,3-triazolyl, 1-, and 2-tetrazolyl fragments in 41-76% yield. The structures of the obtained compounds have been elucidated by means of HRESI-MS, H and C{H} NMR, and single crystal X-ray diffraction {for 3'-[4-(1-5-,-dimethylaminocarbonylmethyltetrazol-1-yl)-1-1,2,3-triazol-1-yl]thymidine }. biological evaluation of the prepared compounds has been performed; they have exhibited low activity against phenotypic HIV-1.

Peroxide route to the synthesis of ultrafine CeO-FeO nanocomposite via successive ionic layer deposition.

An ultrafine α-CeO-α-FeO nanocomposite was prepared from the ultradispersed nanoparticles of cerium (IV) and iron (III) amorphous hydroxides heat-treated at 600 °С and 900 °С in the air. The initial composites were obtained by the successive ionic layer deposition (SILD) method. According to scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX) and powder X-ray diffraction (PXRD), the cerium/iron ratio in the synthesized nanocomposite is close to 1:2, and the α-CeO and α-FeO nanocrystals are isometrically shaped and have an average size of 4 ± 1 and 7 ± 1 nm (600 °С) and 24 ± 2 and 35 ± 3 nm (900 °С), respectively.

Advanced palladium free approach to the synthesis of substituted alkene oxindoles aluminum-promoted Knoevenagel reaction.

A synthetic route for the synthesis of C24, as well as for the design of focused libraries of direct AMPK activators was developed based on a convergent strategy. The proposed scheme corresponds to the current trends in C-H bond functionalization. The use of aluminum isopropoxide for the Knoevenagel condensation of oxindole with benzophenones is a noticeable point of this work.

Heat-Resistant Ferroelectric-Polymer Nanocomposite with High Dielectric Constant.

The high dielectric constant ferroelectric-polymer nanocomposite was developed for producing the heat-resistant and chemical stable planar layers. According to the composite coatings formation conditions, the following value ranges of dielectric constant and loss factor were received: 30⁻400 for dielectric constant and 0.04⁻0.

Molecular Factors Involved in Spinal Muscular Atrophy Pathways as Possible Disease-modifying Candidates.

Spinal Muscular Atrophy (SMA) is a neuromuscular disorder caused by mutations in the SMN1 gene. Being a monogenic disease, it is characterized by high clinical heterogeneity. Variations in penetrance and severity of symptoms, as well as clinical discrepancies between affected family members can result from modifier genes influence on disease manifestation.

Identification of small-molecule elastase inhibitors as antagonists of IL-36 cytokine activation.

IL-1 family cytokines act as apical initiators of inflammation in many settings and can promote the production of a battery of inflammatory cytokines, chemokines and other inflammatory mediators in diverse cell types. IL-36α, IL-36β and IL-36γ, which belong to the extended IL-1 family, have been implicated as key initiators of skin inflammation in psoriasis. IL-36γ is highly upregulated in lesional skin from psoriatic individuals, and heritable mutations in the natural IL-36 receptor antagonist result in a severe form of psoriasis.

Bicyclic Piperazine Mimetics of the Peptide β-Turn Assembled via the Castagnoli-Cushman Reaction.

5-Oxopiperazine-2-carboxamides and respective carboxylic acids (obtained by the Castagnoli-Cushman reaction of protected iminodiacetic anhydride) were converted into cis- and trans-configured bicyclic piperazines containing two stereogenic centers. The latter are not only well-established mimetics of peptide β-turn but also attractive, high-F cores for drug design in general. The methodology was applied to the preparation of ring-expanded version of bicyclic piperazines not described in the literature.

Design, in silico prioritization and biological profiling of apoptosis-inducing lactams amenable by the Castagnoli-Cushman reaction.

Five lactam chemotypes amenable by the Castagnoli-Cushman reaction of imines and cyclic anhydrides have been investigated for their ability to activate p53 tumor suppressing transcription factor thus induce apoptosis in p53 cancer cells. A virtual library of 1.07 million chemically diverse compounds based on these scaffolds was subjected to in silico screening first.

Speciation network in Laurasiatheria: retrophylogenomic signals.

Rapid species radiation due to adaptive changes or occupation of new ecospaces challenges our understanding of ancestral speciation and the relationships of modern species. At the molecular level, rapid radiation with successive speciations over short time periods-too short to fix polymorphic alleles-is described as incomplete lineage sorting. Incomplete lineage sorting leads to random fixation of genetic markers and hence, random signals of relationships in phylogenetic reconstructions.

Improvement of vibrodamping properties of polyvinyl acetate-graphite composites by electron beam processing of the filler.

The effect of electron beam processing (energy 900 keV, absorbed dose in the range from 25 to 600 kGy) of graphite upon the efficiency of its use as a filler in polyvinyl acetate (PVA) based vibrodamping composites is studied. Graphite treatment at optimal doses above 200 kGy is found to provide a significant increase of damping loss factor for these composites at ambient and especially at elevated temperatures. The observed improvement of vibrodamping properties correlates with the increase in the content of Broensted centers (hydroxyl groups) on modified graphite surface probably due to the additional bonding of the filler particles with each other and PVA binder.

Special Issue on Cell Death: Murder, mystery (and a little bit of mayhem) in Manhattan.

This Special Issue on Cell Death comprises a series of 12 reviews that span a broad spectrum of topics within highly active research areas in the cell death field. We hope that you will find these pieces to be of interest; we certainly found them to be fresh and engaging and we are grateful to their authors for taking the time to write for The FEBS Journal.

Incomplete Lineage Sorting and Hybridization Statistics for Large-Scale Retroposon Insertion Data.

Ancient retroposon insertions can be used as virtually homoplasy-free markers to reconstruct the phylogenetic history of species. Inherited, orthologous insertions in related species offer reliable signals of a common origin of the given species. One prerequisite for such a phylogenetically informative insertion is that the inserted element was fixed in the ancestral population before speciation; if not, polymorphically inserted elements may lead to random distributions of presence/absence states during speciation and possibly to apparently conflicting reconstructions of their ancestry.

Photometric method for determination of acidity constants through integral spectra analysis.

An express method for determination of acidity constants of organic acids, based on the analysis of the integral transmittance vs. pH dependence is developed. The integral value is registered as a photocurrent of photometric device simultaneously with potentiometric titration.

A new synthesis of benzo[b]thiophene-2-thiolates and their derivatives via base-promoted transformation of 4-(2-mercaptophenyl)-1,2,3-thiadiazoles.

A reaction of 4-(2-mercaptophenyl)-1,2,3-thiadiazoles with an oxidant in the presence of 1.1 equiv of base afforded good yields of benzo[4,5]thieno[3,2-d][1,2,3]thiadiazoles via the intramolecular oxidative nucleophilic substitution of a hydrogen (ONHS) pathway. The reaction of 4-(2-mercaptophenyl)-1,2,3-thiadiazoles in the presence of ≥2 equiv of base gave 2-mercaptobenzo[b]thiophenes via an anionic ring-opening/ring-closure pathway.

A novel synthesis of benzo[b]selenophenes via regioselective intramolecular transformation of 4-(3-nitroaryl)-1,2,3-selenadiazoles.

Base-promoted transformation of 4-(3-nitroaryl)-1,2,3-selenadiazoles via intermediate formation of eneselenolates followed by 5-exo-trig cyclization is reported. The regiochemistry of the intramolecular cyclization is condition-dependent. In the presence of an oxidant, the oxidative nucleophilic substitution of the hydrogen (ONSH, S(N)Ar(H)) pathway, by oxidative aromatization of the rapidly formed σ(H)-adduct, takes place.

Transport properties and electroanalytical response characteristics of drotaverine ion-selective sensors.

The construction and electroanalytical response characteristics of poly(vinyl chloride) matrix ion-selective sensors (ISSs) for drotaverine hydrochloride are described. The membranes incorporate ion-association complexes of drotaverine with tetraphenylborate, picrate, tetraiodomercurate, tetraiodobismuthate, Reinecke salt, and heteropolycompounds of Keggin structure-molybdophosphoric acid, tungstophosphoric acid, molybdosiliconic acid and tungstosiliconic acid as electroactive materials for ionometric sensor controls. These ISSs have a linear response to drotaverine hydrochloride over the range 8 x 10(-6) to 5 x 10(-2) mol L(-1) with cationic slopes from 51 to 58 mV per concentration decade.