Search results for "DISCOVERY"

showing 10 items of 4119 documents

Cytotoxic labdane diterpenes and bisflavonoid atropisomers from leaves of Araucaria bidwillii

2017

Abstract Chemical investigation of a methanolic extract of leaves from Araucaria bidwillii (Araucariaceae) from Egypt afforded four new labdane diterpenoidal metabolites (1–4) together with one known diterpene, 7-oxocallitrisic acid (5), two triterpenoidal metabolites, 2-O-acetyl-11-keto-boswellic acid (6) and β-sitosterol-3-O-glucopyranoside (7), phloretic acid (8), and two methylated bisflavonoids, agathisflavone-4′,7,7″-trimethyl ether (9) and cupressuflavone-4′,7,7″-trimethyl ether (10). The new metabolites 1–4 were unambiguously identified by applying extensive 1D and 2D NMR spectroscopic studies as well as HRESIMS. The relative and absolute configurations of 1–4 were determined using …

Atropisomer010405 organic chemistryStereochemistryOrganic ChemistryEtherAraucaria bidwillii010402 general chemistryAntimicrobial01 natural sciencesBiochemistryfood.food0104 chemical sciencesLabdanechemistry.chemical_compoundfoodTermészettudományokchemistryDrug DiscoveryOrganic chemistryPhloretic acidDiterpeneKémiai tudományokTwo-dimensional nuclear magnetic resonance spectroscopyTetrahedron
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�ber den Einflu� vegetativ wirksamer Pharmaka auf die Folgen der Injektion von Thiopental in die Arteria femoralis der Ratte

1962

An 150 Ratten wurde der Einflus vegetativ wirksamer Pharmaka (Reserpin, Guanethidin, Chlorisondamin, Dibenamin, Atropin, Hydroxyphenylaminoathanol) auf die Folgen einer Injektion von Thiopental in die Femoralarterie untersucht. Keine der gepruften Substanzen verminderte die durch Thiopental verursachten lokalen Schadigungen.

Autonomic Drugsbusiness.industryAnesthesiamedicine.arteryDrug DiscoverymedicineMolecular MedicineGeneral MedicineFemoral arterybusinessGenetics (clinical)Klinische Wochenschrift
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Glycosyl azides as building blocks in convergent syntheses of oligomeric lactosamine and Lewisx saccharides

1997

Abstract Oligosaccharides containing type 2 lactosamine repeating units, e.g. neo-lacto-octaose and trimeric Lewis x derivatives, are constructed using neo-lactosamine azide building blocks. The azido group provides a favorable protection of the anomeric position which is stable to versatile protecting group manipulations and glycosylation reactions. On the other hand, glycosyl azides can be converted into glycosyl fluorides via a 1,3-dipolar cycloaddition with di- tert -butyl-acetylenedicar☐ylate and subsequent treatment of the resulting N -glycosyl triazoles with hydrogen fluoride-pyridine complex. Activation of the lactosamine fluorides with Lewis acids affords the possibility to extend …

AzidesMagnetic Resonance SpectroscopyGlycosylationChemistryStereochemistryMolecular Sequence DataOrganic ChemistryClinical BiochemistryChemical glycosylationDisaccharideLewis X AntigenPharmaceutical ScienceAmino SugarsBiochemistrychemistry.chemical_compoundCarbohydrate SequenceDrug DiscoveryCarbohydrate ConformationMolecular MedicineGlycosylLewis acids and basesAzideGlycosyl donorProtecting groupMolecular BiologyBioorganic & Medicinal Chemistry
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A Theoretical Study of the Relationship between the Electrophilicity ω Index and Hammett Constant σp in [3+2] Cycloaddition Reactions of Aryl Azide/A…

2016

The relationship between the electrophilicity ω index and the Hammett constant σp has been studied for the [2+3] cycloaddition reactions of a series of para-substituted phenyl azides towards para-substituted phenyl alkynes. The electrophilicity ω index—a reactivity density functional theory (DFT) descriptor evaluated at the ground state of the molecules—shows a good linear relationship with the Hammett substituent constants σp. The theoretical scale of reactivity correctly explains the electrophilic activation/deactivation effects promoted by electron-withdrawing and electron-releasing substituents in both azide and alkyne components.

AzidesSubstituentPharmaceutical ScienceAlkynearylazides010402 general chemistryPhotochemistry01 natural sciencesArticleAnalytical Chemistrylcsh:QD241-441electrophilicity indexchemistry.chemical_compound[2+3] cycloaddition reactionslcsh:Organic chemistryComputational chemistryDrug DiscoveryReactivity (chemistry)Physical and Theoretical Chemistrychemistry.chemical_classificationsubstituent effects010405 organic chemistryArylOrganic Chemistry[2+3] cycloaddition reactions; arylazides; arylalkynes; substituent effects; electrophilicity index; Hammett constantsCycloaddition0104 chemical sciencesModels ChemicalchemistryChemistry (miscellaneous)AlkynesElectrophilearylalkynesHammett constantsMolecular MedicineDensity functional theoryAzideMolecules; Volume 21; Issue 11; Pages: 1434
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Microwave-Assisted Synthesis of New Selenazole Derivatives with Antiproliferative Activity

2013

New aryl-hydrazinyl-1,3-selenazole and aroyl-hydrazonyl-1,3-selenazoles were synthesized via Hantzsch type condensation reactions of selenosemicarbazides with α-halogenocarbonyl derivatives, under classical versus microwave heating conditions. Excellent yields and shorter reaction times were obtained under irradiation conditions. The structures of the synthesized compounds were assigned based on spectroscopic data (FT-IR, 1 H-NMR), MS and elemental analysis. Selenazole derivatives were screened for their anti-proliferative effects against two leukemia cell lines (CCRF-CEM and HL60) and three carcinoma cell lines (MDA-MB231, HCT116 and U87MG).

AzolesHL60Pharmaceutical ScienceAntineoplastic AgentsHL-60 CellsMicrowave assistedArticleLeukemia cell lineAnalytical Chemistrylcsh:QD241-441Inhibitory Concentration 50chemistry.chemical_compoundlcsh:Organic chemistryselenazole; microwave assisted synthesis; cytotoxicityCell Line TumorOrganoselenium CompoundsCarcinoma CellDrug DiscoveryHumansPhysical and Theoretical ChemistryMicrowavesCell ProliferationOrganic ChemistryselenazoleHCT116 CellsCondensation reactionCombinatorial chemistrychemistryChemistry (miscellaneous)Elemental analysisMicrowave heatingcytotoxicityMolecular Medicinemicrowave assisted synthesisMolecules
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Investigations concerning the COX/5-LOX inhibiting and hydroxyl radical scavenging potencies of novel 4,5-diaryl isoselenazoles

2007

The aim of this study was to investigate 4,5-diaryl isoselenazoles as multiple target non-steroidal anti-inflammatory drugs (MTNSAIDs) which can intervene into the inflammatory processes via different mechanisms of action creating a new class of compounds. Here we describe the synthesis of COX/LOX inhibitors which additionally reduce the level of reactive oxygen species, such as hydroxyl radicals which are well known for supporting inflammation processes in Parkinson's disease, Alzheimer's disease and rheumatoid arthritis.

AzolesModels MolecularMagnetic Resonance SpectroscopyAntioxidantStereochemistryRadicalmedicine.medical_treatmentInflammationPharmacologychemistry.chemical_compoundDrug DiscoverymedicineCyclooxygenase InhibitorsLipoxygenase InhibitorsSelenium CompoundsPharmacologychemistry.chemical_classificationReactive oxygen speciesbiologyChemistryEbselenOrganic ChemistryFree Radical ScavengersGeneral MedicineEnzyme inhibitorArachidonate 5-lipoxygenasebiology.proteinHydroxyl radicalmedicine.symptomEuropean Journal of Medicinal Chemistry
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Discovery of 5-benzyl-3-phenyl-4,5-dihydroisoxazoles and 5-benzyl-3-phenyl-1,4,2-dioxazoles as potent firefly luciferase inhibitors.

2013

Luciferase reporter assays are commonly used in high-throughput screening methods. Here, we report new firefly luciferase (FLuc) inhibitors based on 5-benzyl-3-phenyl-4,5-dihydroisoxazoles and 5-benzyl-3-phenyl-1,4,2-dioxazoles, which showed up as "false positives" in a luciferase reporter gene-based assay for nuclear receptor antagonists. The inhibition was shown to be noncompetitive for both natural enzyme substrates (d-luciferin and ATP) and selective to FLuc and proven to arise from a direct interaction between the enzyme and the inhibitor. Of the 63 evaluated compounds, 28 showed significantly better inhibition potency than the well-known inhibitor resveratrol (IC(50) = 59 nM), with fi…

AzolesModels MolecularMagnetic Resonance SpectroscopyStereochemistryDrug Evaluation PreclinicalResveratrolCell Linechemistry.chemical_compoundInhibitory Concentration 50Drug DiscoveryScreening methodIc50 valuesPotencyAnimalsLuciferaseEnzyme InhibitorsLuciferasesIC50ta116chemistry.chemical_classificationFirefliesEnzymechemistryNuclear receptorBiochemistryMolecular MedicineJournal of medicinal chemistry
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Synthesis and in vitro antimicrobial activities of new (cyano-NNO-azoxy) pyrazole derivatives

2011

The antibacterial and antifungal activity of a series of products, in which the 1,5-dimethyl-4-(cyano- NNO-azoxy)pyrazol-3-yl and 1,3-dimethyl-4-(cyano-NNO-azoxy)pyrazol-5-yl moieties were linked to pyridine, pyrazole, isoxazole, thiophene and the furan ring, were examined. No molecule displayed activity against the Gram-negative bacteria tested. Conversely, some compounds displayed activity against two Staphylococcus aureus strains, including the methicillin resistant strain. All compounds displayed interesting antifungal activity, the most active compound of the series being the thiophene derivative 7a. This compound’s activity against Candida krusei and Candida glabrata (MIC = 0.25 and 0…

AzoxyStaphylococcus aureusAntifungal AgentsStereochemistryClinical BiochemistryPharmaceutical ScienceMicrobial Sensitivity TestsPyrazoleBiochemistryChemical synthesisAntifungal activity Pyrazole Azole sistance Cyano-NNO-azoxy Thiophenechemistry.chemical_compoundAnti-Infective AgentsThiopheneCandida kruseiNitrilesDrug DiscoveryThiopheneAntifungal activityIsoxazoleAntifungal activity; Pyrazole; Azole resistance; Cyano-NNO-azoxy; Thiophene.Molecular BiologyCandidaMolecular StructurebiologyCandida glabrataOrganic ChemistryBiological activitybiology.organism_classificationSettore CHIM/08 - Chimica FarmaceuticachemistryCyano-NNO-azoxyPyrazoleAzole resistancePyrazolesMolecular MedicineAzo Compounds
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Asymmetric Michael Addition in Synthesis of β-Substituted GABA Derivatives

2022

γ-Aminobutyric acid (GABA) represents one of the most prolific structural units widely used in the design of modern pharmaceuticals. For example, β-substituted GABA derivatives are found in numerous neurological drugs, such as baclofen, phenibut, tolibut, pregabalin, phenylpiracetam, brivaracetam, and rolipram, to mention just a few. In this review, we critically discuss the literature data reported on the preparation of substituted GABA derivatives using the Michael addition reaction as a key synthetic transformation. Special attention is paid to asymmetric methods featuring synthetically useful stereochemical outcomes and operational simplicity. This research was funded by the National Na…

Baclofenasymmetric Michael additionγ-aminobutyric-acid derivativesOrganic ChemistryPregabalinPharmaceutical ScienceStereoisomerismQuímica farmacèuticapharmaceuticalsneurological drugsAnalytical ChemistryReaccions químiqueschiral auxiliariesChemistry (miscellaneous)Drug DiscoveryMolecular Medicineenantioselective organocatalysisPhysical and Theoretical Chemistrygamma-Aminobutyric AcidMedicaments
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The widespread presence of a family of fish virulence plasmids in Vibrio vulnificus stresses its relevance as a zoonotic pathogen linked to fish farms

2021

Vibrio vulnificus is a pathogen of public health concern that causes either primary septicemia after ingestion of raw shellfish or secondary septicemia after wound exposure to seawater. In consequence, shellfish and seawater are considered its main reservoirs. However, there is one aspect of its biology that is systematically overlooked: its association with fish in its natural environment. This association led in 1975 to the emergence of a zoonotic clade within phylogenetic lineage 2 following successive outbreaks of vibriosis in farmed eels. Although this clade is now worldwide distributed, no new zoonotic clades were subsequently reported. In this work, we have performed phylogenetic, ge…

Bacterial ZoonosesEpidemiologyanimal diseasesFish farmingImmunologyVirulenceVibrio vulnificusAquacultureBiologyphylogenyMicrobiologyMicrobiologyFish DiseasesPlasmidVirologyDrug DiscoverymedicineAnimalsHumansPathogenZoonotic pathogenVibrio vulnificusShellfishintegumentary systemVirulenceZoonosisFishesGeneral Medicinevibriosiszoonosisbacterial infections and mycosesmedicine.diseasebiology.organism_classificationvirulence plasmidInfectious DiseasesVibrio InfectionsV. vulnificusParasitologyResearch ArticlePlasmids
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