Highly Stereoselective Synthesis and Biological Properties of Nucleoside Analogues Bearing a Spiro Inserted Oxirane Ring

Abstract

Starting from 2′,5′-di-O-TBDMS-3′-ketouridine 1 or its thymine analogue 2, both xylo (3–10) and ribo (20) epimers of a series of 3″-substituted 3′-spironucleosides have been obtained in good yields and with a total stereoselectivity. Most new compounds were moderately cytotoxic with in some cases slightly selective antiproliferative activities. None of these compounds was active against HIV, but some other antiviral activities against HSV-2, CMV, EBV, or VZV, in the micromolar range, were noted in specific cases.     

A 2015 survey of established or potential epigenetic biomarkers for the accurate detection of human cancers

Context The silencing or activation of cancer-associated genes by epigenetic mechanisms can ultimately lead to the clonal expansion of cancer cells. Objective The aim of this review is to summarize all relevant epigenetic biomarkers that have been proposed to date for the diagnosis of some prevalent human cancers. Methods A Medline search for the terms epigenetic biomarkers, human cancers, DNA methylation, histone modifications and microRNAs was performed. Results One hundred fifty-seven relevant publications were found and reviewed. Conclusion To date, a significant number of potential epigenetic cancer biomarkers of human cancer have been investigated, and some have advanced to clinical implementation.     

Cyberlindnera fabianii: primer aislamiento clínico en Chile

BackgroundAlthough considered an unusual etiological agent, Cyberlindnera (Candida) fabianii has been related to septicemia in several reports in recent years. Its doubtful or uncertain identification when using tests such as CHROMagar Candida, API® Candida, API® ID32C or VITEK® MS, leads to an underestimation of the cases produced by this yeast.AimsTo report the first isolation of C. fabianii in Chile and its identification.MethodsThe sequencing of the internal transcribed spacer region (ITS) was performed. Antifungal susceptibility profiles were obtained by means of the broth microdilution technique.ResultsThe identification was only reached by sequencing the ITS regions, which shows the limited usefulness of the conventional techniques in the identification of some yeast species. A dendrogram shows the phylogenetic relationship of the isolated strain with some other yeast species.ConclusionIn the identification of fastidious microorganisms or microorganisms whose identification is not completely reliable when using classical or even advanced methodologies, such as mass spectrometry, sequencing techniques are essential.     

Using matrix summation method for three dimensional dose calculation in brachytherapy

AimThe purpose of this study is to calculate radiation dose around a brachytherapy source in a water phantom for different seed locations or rotation the sources by the matrix summation method.BackgroundMonte Carlo based codes like MCNP are widely used for performing radiation transport calculations and dose evaluation in brachytherapy. But for complicated situations, like using more than one source, moving or rotating the source, the routine Monte Carlo method for dose calculation needs a long time running.Materials and methodsThe MCNPX code has been used to calculate radiation dose around a ¹⁹²Ir brachytherapy source and saved in a 3D matrix. Then, we used this matrix to evaluate the absorbed dose in any point due to some sources or a source which shifted or rotated in some places by the matrix summation method.ResultsThree dimensional (3D) dose results and isodose curves were presented for ¹⁹²Ir source in a water cube phantom shifted for 10 steps and rotated for 45 and 90° based on the matrix summation method. Also, we applied this method for some arrays of sources.ConclusionThe matrix summation method can be used for 3D dose calculations for any brachytherapy source which has moved or rotated. This simple method is very fast compared to routine Monte Carlo based methods. In addition, it can be applied for dose optimization study.     

Tryptophol Metabolism by a Species of Arthrobacter

The stereochemistry of some dihydrofurano-isoflavones previously isolated from white lupin roots, or obtained following fungal metabolism of prenylated isoflavones, was investigated using CD spectroscopy. The osmate ester/pyridine complex of dextrorotatory lupinisoflavone A (1) exhibited a positive CD Cotton effect at 480 nm, indicating a side-structure configuration (S at C- 2″), opposite to that of natural rotenone (9), which afforded a negative Cotton effect at 474 nm (R- configuration at C-2′ on the side structure [ring E]). The stereochemistry of the laevorotatory luteone metabolite BC-1 (2) and lupinisoflavone D (4) (both ^-configuration at C-2″) was similarly determined after converting to the corresponding dehydrate (10) or trimethyl-dehydrate (1b, 10a).     

Synthesis of some N-[4-(benzothiazole-2yl) phenyl]-2-aryloxyacetamide derivatives and their anticancer activities

In this study, some N-[4-(Benzothiazole-2-yl) phenyl]-2-aryloxyacetamide derivatives were prepared by reacting N-[4-(benzothiazole-2yl)phenyl]-2-chloroacetamide and different substituent phenol or thiophenol derivatives. The anticancer activities of the compounds obtained were investigated. It was observed that some of the compounds, namely 25 and 38, showed notable anticancer activity.     

Renesting by male Dotterel Charadrius morinellus after successfully rearing chicks

Although some waders (Charadrii) are known regularly to attempt to rear 2 broods in some summers (e.g. Ringed Plover Charadrius hiaticula, Little Ringed Plover Charadrius dubius ^l), this ability is not associated with Palearctic waders breeding at higher latitudes, except where one or more clutches are left in the sole care of previous mates. This note documents an attempt made by a male Dotterel to raise a second brood after its first brood of young became independent.     

Effects of boron-containing compounds in the fungal kingdom

BackgroundThe number of known boron-containing compounds (BCCs) is increasing due to their identification in nature and innovative synthesis procedures. Their effects on the fungal kingdom are interesting, and some of their mechanisms of action have recently been elucidated.MethodsIn this review, scientific reports from relevant chemistry and biomedical databases were collected and analyzed.ResultsIt is notable that several BCC actions in fungi induce social and economic benefits for humans. In fact, boric acid was traditionally used for multiple purposes, but some novel synthetic BCCs are effective antifungal agents, particularly in their action against pathogen species, and some were recently approved for use in humans. Moreover, most reports testing BCCs in fungal species suggest a limiting effect of these compounds on some vital reactions.ConclusionsNew BCCs have been synthesized and tested for innovative technological and biomedical emerging applications, and new interest is developing for discovering new strategic compounds that can act as environmental or wood protectors, as well as antimycotic agents that let us improve food acquisition and control some human infections.     

SYNTHESIS AND ANTI-HIV ACTIVITY OF THYMIDINE ANALOGUES BEARING A 4′-CYANOVINYL GROUP AND SOME DERIVATIVES THEREOF

Treatment of 3′-O-tert-butyldimethylsilyl-2′,5′-dideoxy-5′-oxothymidine (4) with potassium or magnesium nitromethanide afforded in good yield the resolvable epimeric mixture of the expected blocked nitronucleosides 5 which upon dehydration led to the corresponding E-nitroenofuranosylthymidine 6. Nucleophilic attack of cyanide onto the nitrovinyl group led to a nucleoside analogue bearing a terminal 1-cyanovinyl group (7), a soft electrophilic group which, upon reaction with benzeneselenol, underwent a conjugate addition to the phenylselenonucleoside derivative 9. All these compounds, eventually de-O-silylated, were subject of in vitro biological testing, some exhibiting interesting cytotoxic or antiviral properties.     

Creating ephemeral resources: how long do the beneficial effects of grass cutting last for birds?

CapsuleBeneficial effects of cutting grass are relatively short-lived for a range of bird species.

AimsTo investigate how cutting affects a range of birds occurring on farmland, how long these effects last, and whether there is any effect of the timing of cutting operations.

MethodsWe surveyed birds on 33 grass fields on three farms in northern England, both before and after agricultural cutting operations. The data were then modelled using generalized linear mixed models (GLMMs).

Results Species relying on below-ground invertebrates (e.g. corvid species) prefer cut swards, while some species make greater use of longer grass swards (e.g. pheasant). Use of fields after cutting declined by 50 % by day 11 for corvids, by day 8 for aerial feeders (e.g. hirundines), by day 6 for gulls, and by day 4 for kestrels.

ConclusionsWe recorded mainly common, generalist species that make use of agricultural grassland. The foraging behaviour of these species is similar to other, rarer or declining species, and so our findings can be extrapolated to a range of farmland birds. However, it is important to note that some studies indicate direct negative effects of cutting on some species not found in our surveys.     

D-xylo and Lyxofuranonucleosides Reviewed: Some Suggestions on The Mechanism of Activity of Antiviral Nucleosides

Abstract

D-Xylo and Lyxofuranonucleosides have not been extensively studied. Therefore in order to perform a systematic Structure-Antiviral Activity Relationship of the nucleoside analogs we have first synthesized their α and β anomers, some of them being unknown or their structure doubtful in the literature.     

A New Synthesis of (E,E)-8, 10-Dodecadien-1-ol,Sex Pheromone of Codling Moth

A methanol-utilizing bacterium, which produced red to pink pigments and assimilated methanol via icl^- serine pathway, was isolated from soil and tentatively designated as Pseudomonas MS 31. This bacterium produced L-serine when glycine was added to the growth medium at the late exponential phase of growth. The cells showed high L-serine degradation activity. Chelating agents and some metal ions, which inhibited L-serine degradation, stimulated the L-serine accumulation. In the presence of 0.1 ? 1 mM EDTA, o-phenanthroline, 8-hydroxyquinoline, α,α'-dipyridyl, cobalt sulfate or nickel sulfate, this bacterium produced 0.7?2.1mg L-serine from 4mg glycine per ml culture.     

3,5-Bis(Phenylmethylene)-1-(N-arylmaleamoyl)-4-piperidones: A Novel Group of Cytotoxic Agents

A series of novel 3,5-bis(phenylmethylene)-1-(N-arylmaleamoyl)-4-piperidones 3 have been synthesized which displayed potent cytotoxicity towards human Molt 4/C8 and CEM T-lymphocytes as well as murine P388 and L1210 leukemic cells. In contrast, the related N-arylmaleamic acids 4 possessed little or no cytotoxicity in these four screens. Molecular modeling revealed certain interplanar and bond angles and interatomic distances which were perceived to contribute to the observed bioactivity as well as providing suggestions for future structural modifications of the piperidones 3. Evaluation of representative compounds in series 3 and 4 on the activity of human N-myristoyltransferase revealed that, at the maximum concentration utilized, namely 250?μM, only weak inhibiting properties were displayed by some of the compounds in series 4. Various members of series 3 and 4 were well tolerated in mice.     

Reversible Inhibition of Enzymatic Systems Involving Covalent Intermediates

Abstract

Reversible inhibition phenomena are analyzed for enzymatic systems involving covalent intermediates, where the inhibitor can bind to the pure enzyme, the Henri-Michaelis complex or the covalent intermediate, or to two or three of these enzyme forms. Classical competitive, non-competitive or un-competitive phenomena can be observed in some cases but unexpected features are also observed. Complex phenomena sometimes prevail where increased k_cat/K_m values can be accompanied by decreased or increased k_cat values.     

Cryptogamic section report for 1969

Summary

From some 50 samples collected in many parts of Scotland in 1996, 15 sites have been selected as containing rare or at least unusual desmids. The sites are listed and the desmids, some new records for the British Isles, are illustrated.     

Phytosterols of marine algae: Insights into the potential health benefits and molecular pharmacology

BackgroundMarine algae are rich in some unique biologically active secondary metabolites having diverse pharmacological benefits. Of these, sterols comprise a group of functional lipid compounds that have attracted much attention to natural product scientists.PurposeThis review was aimed to update information on the health effects of algae-derived phytosterols and their molecular interactions in various aspects of human health and diseases and to address some future perspectives that may open up a new dimension of pharmacological potentials of algal sterols.MethodsA literature-based search was carried out to retrieve published research information on the potential health effects of algal phytosterols with their pharmacological mechanisms from accessible online databases, such as Pubmed, Google Scholar, Web of Science, and Scopus, using the key search terms of ‘marine algae sterol’ and ‘health potentials such as antioxidant or anti-inflammatory or anti-Alzheimer's or anti-obesity or cholesterol homeostasis or hepatoprotective, antiproliferative, etc.’ResultsPhytosterols of marine algae, particularly fucosterol, have been investigated for a plethora of health benefits, including anti-diabetes, anti-obesity, anti-Alzheimer's, antiaging, anticancer, and hepatoprotection, among many others, which are attributed to their antioxidant, anti-inflammatory, immunomodulatory and cholesterol-lowering properties, indicating their potentiality as therapeutic leads. These sterols interact with enzymes and various other proteins that are actively participating in different cellular pathways, including antioxidant defense system, apoptosis and cell survival, metabolism, and homeostasis.ConclusionIn this review, we briefly overview the chemistry, pharmacokinetics, and distribution of algal sterols, and provide critical insights into their potential health effects and the underlying pharmacological mechanisms, beyond the well-known cholesterol-lowering paradigm.     

Controversial effect on Erk activation of some cytotoxic drugs in human LOVO colon cancer cells

The use of some classic antibiotics was recently shown to inhibit growth and to induce apoptosis in human LOVO colon cancer cells. In this study, we describe that ciprofloxacin (CI), trimebutine maleate (COL) and tiemonium methylsulfate (VIS) greatly inhibit cell proliferation in vitro. Proliferation inhibition reached its maximum at 10^–4?M, 10^–3?M and 10^–2?M, respectively, for COL, CI and VIS. Moreover, phospho-extracellular-regulated kinase was totally abrogated in non-apoptotic cytotoxicity of VIS but decreases or increases in the apoptotic inhibition, respectively, of COL and CI treatments.

Abbreviations: CI: ciprofloxacin; COL: trimebutine maleate; VIS: tiemonium methylsulfate; MAPK/Erk: mitogen-activated protein kinases/extracellular-regulated kinase     

我国医药分开政策目的及其策略分析

目的 进一步明确医药分开政策目的及策略。方法 采用文献回顾性研究法,对医药利益链条及其形成原因,以及解决策略进行系统性地总结和分析。结果 现有研究一是认为医疗服务提供方拥有垄断地位造成利益链条存在,因而提出消除垄断;二是认为扭曲的“白色”或不良的“灰色”激励机制造成利益链条存在,因而提出完善“白色”或消除“灰色”激励机制的综合策略。结论 医药利益链条产生更深层次的原因是,非营利性的公立医疗机构不合理地追求经济利益,医生采用不合理方式追求部分合理经济利益。因此,医药分开目的应是让公立医疗机构真正成为非营利机构,使医生依靠技术获得合理的经济回报,让公立医疗机构、医生、政府、患者、药品企业及流通商间激励相容。建议采用外部补偿和内部薪酬制度为重点的综合改革策略,形成各利益相关方激励相容的良好局面,自然消除公立医疗机构、医生与药品销售间利益链条。     

Photodimerizations of hydroxy- and benzoylated 4-azachalcones and quantum chemical investigation of the reactions

Photodimerization reactions of compounds 4–6 gave four new cyclobutane-containing compounds (7–9) with full control over the stereochemistry at the four stereogenic centers. These new cyclobutane-containing compounds had β-truxinic (7a), δ-truxinic (7b and 9), and ε-truxillic (8) structures. However, o-, m-, and p-hydroxy 4-azachalcones (1–3) did not give photochemical cyclization products under any conditions (in solvent or in their solid or molten states). Experimental data suggested the possibility of frontier orbital control over stereochemical behavior, so some theoretical calculations were performed. Full geometrical optimization of compounds 1–9 was performed via DFT B3LYP/6-31⁺G**, and their electronic structures were also investigated. The geometries of the singlet and triplet states were initially optimized by density functional theory (DFT) and the configuration interaction singles (CIS) B3LYP/3-21⁺G** level. An additional calculation was performed for the triplet state using the ground-state geometry. The possible photochemical dimerization products of compounds 7–9 (a–g) and the intrinsic reaction coordinates (IRCs) of the reactions of compounds 4–6 were calculated theoretically by the DFT/3-21⁺G** method. The configurations (reactant, transition state, product, and reaction pathway) corresponding to the stationary points (minima or saddle points) were determined. The intrinsic reaction coordinates were followed to verify the energy profiles that connect each TS to the appropriate local minimum. The dimeric products expected from the calculations coincided with the dimers produced experimentally.