Search results for "DISCOVERY"

showing 10 items of 4119 documents

Agkistrodon ameliorates pain response and prevents cartilage degradation in monosodium iodoacetate-induced osteoarthritic rats by inhibiting chondroc…

2019

Abstract Ethnopharmacological relevance Osteoarthritis (OA), characterized by joint pain and cartilage degradation, is the most common form of joint disease worldwide but with no satisfactory therapy available. The ethanol extract of Agkistrodon acutus (EAA) has been widely used as a traditional Chinese medicine (TCM) for the treatment of arthralgia and inflammatory diseases, but there is no report regarding its efficacy on OA to date. Here, we determined the effects of EAA on the pain behavior and cartilage degradation in vivo and clarified its target genes and proteins associated with chondrocyte hypertrophy and apoptosis in vitro. Materials and methods In vivo OA model was established by…

Cartilage ArticularMalePainChondrocyte hypertrophyApoptosisOsteoarthritisPharmacologyComplex MixturesChondrocyteRats Sprague-Dawley03 medical and health sciencesAnimal data0302 clinical medicineChondrocytesIn vivoDrug DiscoveryOsteoarthritismedicineAnimalsViability assay030304 developmental biologyPharmacology0303 health sciencesAnalgesicsChemistryCartilageHypertrophymedicine.diseaseIodoacetic Acidmedicine.anatomical_structureApoptosis030220 oncology & carcinogenesisAgkistrodonJournal of ethnopharmacology
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Syntheses of oxygenated spongiane diterpenes from carvone. Synthesis of dorisenone C

2005

Abstract The synthesis of dorisenone C, a representative member of the spongiane-type diterpene family, is described. The synthesis follows a B→AB→ABC→ABCD approach and is based on the initial preparation of the previously known hydroxy-aldehyde 14 (AB rings) from R -(−)-carvone, followed by an intramolecular Diels–Alder reaction between an oxygenated diene moiety and an acetylenic dienophile for the construction of the C ring (compound 22 ), and adequate manipulation of the Diels–Alder adduct functionality for completion of the spongiane framework.

CarvoneDieneStereochemistryOrganic ChemistryBiochemistryAdductTerpenechemistry.chemical_compoundchemistryIntramolecular forceDrug DiscoveryMoietyOrganic chemistryDiterpeneDiels–Alder reactionTetrahedron
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Silicon guided rearrangement of epoxydecalines to spirocyclic compounds. Synthesis of gleenol and axenol from carvone

2005

Abstract The synthesis of the spirocyclic sesquiterpenes (−)-gleenol and (−)-axenol in enantiomerically pure form has been achieved starting from R-(−)-carvone. The key step is the silicon guided acid-promoted rearrangement of a 9-trimethylsilyl-5,6-epoxy-noreudesmane prepared from 3-trimethylsilyldihydrocarvone in several steps involving Robinson annulation, enone deconjugation and epoxidation. Acid treatment of the epoxy-noreudesmane gave a norspiroaxane as the main product, which was used as intermediate for the synthesis of two naturally occurring sesquiterpenes gleenol and axenol.

CarvoneSiliconStereochemistryOrganic Chemistrychemistry.chemical_elementCarbocationBiochemistrychemistry.chemical_compoundchemistryDrug DiscoveryRobinson annulationOrganic chemistryAcid treatmentEnoneTetrahedron
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Synthesis of oxygenated spongiane-type diterpenoids from carvone

2002

Abstract A new diastereoselective approach to oxygenated spongiane diterpenes starting from ( R )-(−)-carvone is described. The carvone is incorporated as the B ring in the final spongiane framework using a B→AB→ABC→ABCD approach, which involves an intramolecular Diels–Alder reaction and the regioselective ring-opening of a dihydrofuran ring as key synthetic steps. The structure of the key intermediate in this approach has been verified by X-ray crystallography.

Carvonechemistry.chemical_compoundChemistryStereochemistryIntramolecular forceOrganic ChemistryDrug DiscoveryRegioselectivityRing (chemistry)BiochemistryTetrahedron Letters
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The Effect of Metal Cations on the Aqueous Behavior of Dopamine. Thermodynamic Investigation of the Binary and Ternary Interactions with Cd2+, Cu2+ a…

2021

The interactions of dopamine [2-(3,4-Dihydroxyphenyl)ethylamine, (Dop−)] with cadmium(II), copper(II) and uranyl(VI) were studied in NaCl(aq) at different ionic strengths (0 ≤ I/mol dm−3 ≤ 1.0) and temperatures (288.15 ≤ T/K ≤ 318.15). From the elaboration of the experimental data, it was found that the speciation models are featured by species of different stoichiometry and stability. In particular for cadmium, the formation of only MLH, ML and ML2 (M = Cd2+; L = dopamine) species was obtained. For uranyl(VI) (UO22+), the speciation scheme is influenced by the use of UO2(acetate)2 salt as a chemical; in this case, the formation of ML2, MLOH and the ternary MLAc (Ac = acetate) species in a …

Catechol; Chemical speciation; Metal complexes; Sequestration; Stability constantsMolecular Structurechemical speciation; metal complexes; catechol; sequestration; stability constantsDopaminePharmaceutical ScienceOrganic chemistrysequestrationmetal complexesSodium Chloridecatecholchemical speciationUranium CompoundsAnalytical Chemistrystability constantsQD241-441Chemistry (miscellaneous)CationsDrug DiscoveryMolecular MedicineThermodynamicsSettore CHIM/01 - Chimica AnaliticaPhysical and Theoretical ChemistryCopperCadmiumMolecules
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Kathepsinaktivit�t im menschlichen Endometrium

1955

Die nach der Methode vonAnson bestimmte Kathepsinaktivitat im menschlichen Endometrium wahrend der verschiedenen Cyclusphasen zeigte keine signifikanten Unterschiede.

CathepsinProteasesDrug DiscoveryMolecular MedicineGeneral MedicineBiologyHuman endometriumMolecular biologyMolecular medicineGenetics (clinical)Human geneticsKlinische Wochenschrift
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Synthesis and activity of phosphinic tripeptide inhibitors of cathepsin C

2004

Phosphinic tripeptide analogues Gly-Xaaψ[P(O)(OH)CH2]-Gly have been developed as inhibitors of cathepsin C (DPP I), a lysosomal, papain-like cysteine protease. The target compounds were synthesised by addition of methyl acrylate to the appropriate phosphinic acids followed by the N-terminus elongation using mixed anhydride procedure. The latter step has been demonstrated to be a suitable method for N-terminal extension of the phosphinic pseudopeptide analogues without requirement of hydroxyphosphinyl protection. The title compounds appeared to be moderate inhibitors of the cathepsin C. However, although designed as transition state analogues, they surprisingly exhibited noncompetitive mode …

Cathepsinchemistry.chemical_classificationnoncompetitive inhibitionStereochemistryphosphinic tripeptidesOrganic ChemistryClinical BiochemistryPharmaceutical ScienceBiological activityPeptideTripeptidePhosphinic AcidsBiochemistryCysteine proteaseChemical synthesisCathepsin CCathepsin CNon-competitive inhibitionchemistryDrug DiscoveryMolecular MedicineProtease InhibitorsOligopeptidesMolecular BiologyBioorganic & Medicinal Chemistry Letters
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Susceptibility of Pseudomonas aeruginosa isolates to ceftazidime is unrelated to the expression of the outer membrane protein OprC.

1997

Previously, it has been postulated that the porin OprC facilitates the diffusion of ceftazidime through the outer membrane of Pseudomonas aeruginosa. To further investigate this claim, the outer membrane protein (OMP) profiles of 22 ceftazidime-susceptible clinical isolates were analyzed. No correlation was found between MIC values and the level of expression of OprC. Further, OprC was either undetectable or expressed in reduced amounts in 12 isolates. In contrast, OprF and OprE were present in all isolates studied. This study suggests that OprC is dispensable for the permeation of ceftazidime through the outer membrane of P. aeruginosa.

CeftazidimePorinsmedicine.disease_causePorinaCeftazidimeMicrobiologyBacterial ProteinsDrug DiscoverymedicineHumansPharmacology (medical)Antibacterial agentPharmacologybiologyPseudomonas aeruginosaGeneral Medicinebiology.organism_classificationCephalosporinsImipenemInfectious DiseasesOncologyMembrane proteinSpainPorinPseudomonas aeruginosaThienamycinsBacterial outer membranePseudomonadaceaemedicine.drugBacterial Outer Membrane ProteinsChemotherapy
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Solid-State Electrochemical Assay of Heme-Binding Molecules for Screening of Drugs with Antimalarial Potential

2013

The interaction between heme and ligands is the basis for a variety of tests aimed at the discovery of antiplasmodial molecules. Two electrochemical methods for the screening of molecules with potential antimalarial activity through heme-binding mechanism are described. The first method is applicable to lipophilic environment, by using solution phase electrochemistry in DMSO solutions of Fe(III)-heme plus the tested compounds at carbon electrodes. This method provides well-defined voltammetric signals, characteristic of the heme-ligand (L) interaction. The second method involves aqueous media at biological pH and the use of voltammetry of immobilized particles, by means of microparticulate …

Cell ExtractsErythrocytesHeme bindingStereochemistryHemeLigandsElectrochemistryFerric CompoundsPraziquantelAnalytical ChemistryAntimalarialsHemoglobinsStructure-Activity Relationshipchemistry.chemical_compoundDrug DiscoveryHumansMoleculeElectrodesHemeVoltammetryQuinineElectrochemical TechniquesHydrogen-Ion ConcentrationCombinatorial chemistryArtemisininsCarbonchemistryElectrodeHemoglobinOxidation-ReductionMacromoleculeAnalytical Chemistry
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Optimization of the Ussing chamber setup with excised rat intestinal segments for dissolution/permeation experiments of poorly soluble drugs.

2016

AbstractContext: Prediction of the in vivo absorption of poorly soluble drugs may require simultaneous dissolution/permeation experiments. In vivo predictive media have been modified for permeation experiments with Caco-2 cells, but not for excised rat intestinal segments.Objective: The present study aimed at improving the setup of dissolution/permeation experiments with excised rat intestinal segments by assessing suitable donor and receiver media.Methods: The regional compatibility of rat intestine in Ussing chambers with modified Fasted and Fed State Simulated Intestinal Fluids (Fa/FeSSIFmod) as donor media was evaluated via several parameters that reflect the viability of the excised in…

Cell Membrane PermeabilityPharmaceutical Science02 engineering and technology030226 pharmacology & pharmacyBile Acids and Salts03 medical and health sciences0302 clinical medicineIn vivoDrug DiscoveryAnimalsHumansDissolutionPharmacologyRat intestineChromatographyUssing chamberChemistryOrganic ChemistryIn vivo absorptionPermeation021001 nanoscience & nanotechnologyRatsIntestinesJejunumSolubilityCaco-2 Cells0210 nano-technologyFederal stateDrug development and industrial pharmacy
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