Search results for "DISCOVERY"

showing 10 items of 4119 documents

Three New Medicagenic Acid Saponins from Polygala micranthaGuill. & Perr.

2011

Three new medicagenic acid saponins, micranthosides A–C (1–3), were isolated from the roots of Polygala micranthaGuill. & Perr., along with six known presenegenin saponins. Their structures were elucidated on the basis of extensive 1D- and 2D-NMR experiments (1H, 13C, DEPT, COSY, TOCSY, NOESY, HSQC, and HMBC) and mass spectrometry as 3-O-β-D-glucopyranosylmedicagenic acid 28-[O-β-D-galactopyranosyl-(14)-O-β-D-xylopyranosyl-(14)-O-α-L-rhamnopyranosyl-(12)-β-D-fucopyranosyl] ester (1), 3-O-β-D-glucopyranosylmedicagenic acid 28-[O-6-O-acetyl-β-D-galactopyranosyl-(14)-O-β-D-xylopyranosyl-(14)-O-α-L-rhamnopyranosyl-(12)-β-D-fucopyranosyl] ester (2), and 3-O-{O-β-D-glucopyranosyl-(13)-O-[β-D-gluc…

biologyChemistryStereochemistryOrganic ChemistryDEPTMass spectrometrybiology.organism_classificationBiochemistryCatalysisPolygalaMedicagenic acidInorganic ChemistryHuman colon cancerDrug DiscoveryPhysical and Theoretical ChemistryCytotoxicityTwo-dimensional nuclear magnetic resonance spectroscopyHeteronuclear single quantum coherence spectroscopyHelvetica Chimica Acta
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Furostane-Type Steroidal Saponins from the Roots ofChlorophytum borivilianum

2008

Four new furostanol steroid saponins, borivilianosides A–D (1–4, resp.), corresponding to (3β,5α,22R,25R)-26-(β-D-glucopyranosyloxy)-22-hydroxyfurostan-3-yl O-β-D-xylopyranosyl-(13)-O-β-D-glucopyranosyl-(14)-O-[α-L-rhamnopyranosyl-(12)]-β-D-galactopyranoside (1), (3β,5α,22R,25R)- 26-(β-D-glucopyranosyloxy)-22-methoxyfurostan-3-yl O-β-D-xylopyranosyl-(13)-O-β-D-glucopyranosyl-(14)-O-[α-L-rhamnopyranosyl-(12)]-β-D-galactopyranoside (2), (3β,5α,22R,25R)-26-(β-D-glucopyranosyloxy)-22-methoxyfurostan-3-yl O-β-D-xylopyranosyl-(13)-O-[β-D-glucopyranosyl-(12)]-O-β-D-glucopyranosyl-(14)-β-D-galactopyranoside (3), and (3β,5α,25R)-26-(β-D-glucopyranosyloxy)furost-20(22)-en-3-yl O-β-D-xylopyranosyl-(13…

biologyChemistryStereochemistryOrganic Chemistrybiology.organism_classificationBiochemistryCatalysisInorganic ChemistrySteroid SaponinsChlorophytum borivilianumDrug DiscoveryFernPhysical and Theoretical ChemistryChlorophytumHelvetica Chimica Acta
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A frozen analogue approach to aminopyridinylimidazoles leading to novel and promising p38 MAP kinase inhibitors.

2012

In this study we report the design, synthesis, and biological evaluation of constrained aminopyridinylimidazoles as p38α MAP kinase inhibitors. The frozen analogue approach focused on the pyridinyl unit, using purine bioisosteres as constrained structure analogues. The identification of the most potent bioisostere was followed by a further derivatization to address hydrophobic region II. In combination with C-2 modifications of the imidazole core, we were able to design highly active inhibitors on the p38α MAP kinase. The inhibitor design presented herein represents a promising and highly efficient advancement of recent stages of development in this class of p38 MAP kinase inhibitors. In co…

biologyChemistryStereochemistryPyridinesp38 mitogen-activated protein kinasesEntropyImidazolesMolecular ConformationCombinatorial chemistryp38 Mitogen-Activated Protein KinasesMolecular conformationMolecular Docking Simulationchemistry.chemical_compoundStructure-Activity RelationshipPurinesMitogen-activated protein kinaseDrug DesignDrug Discoverybiology.proteinMolecular MedicineStructure–activity relationshipBioisostereBiological evaluationJournal of medicinal chemistry
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One-step synthesis of resorcarene dimers composed of two tetra-benzoxazine units

1998

Abstract The condensation of resorcarene 1 with ethylenediamine and an excess of formaldehyde gives, under high dilution conditions, in up to 15% yield the octa-benzoxazine dimer 2 in which two molecules of 1 are connected by four bridges. The structure of 2 has been confirmed by 1 H NMR spectra and MALDI-TOF mass spectra and by hydrolysis of the oxazine rings yielding the secondary amine 3 .

biologyDimerOrganic ChemistryEthylenediamineResorcinarenebiology.organism_classificationBiochemistrychemistry.chemical_compoundchemistryDrug DiscoveryPolymer chemistryMass spectrumProton NMROrganic chemistryTetraMoleculeAmine gas treatingTetrahedron Letters
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Efficient gene therapy based targeting system for the treatment of inoperable tumors

2012

Background A considerable percentage of tumors are not amenable to surgery. We have designed a simple and powerful targeting system that offers an alternative option for the multi-component pre-targeting strategies used clinically. This targeting system can be used for any type of solid tumors independent of the tumor type, thereby omitting the need to engineer unique antibodies for each specific application or tumour type. In the present study, we show the expression of a chimeric fusion protein, which contains the low-density lipoprotein receptor transmembrane domains and avidin, after local gene transfer and its ability to bind biotinylated compounds in vivo. Methods Semliki Forest virus…

biologyGenetic enhancementSemliki Forest virusbiology.organism_classificationmedicine.diseaseFusion proteinMolecular biologyTargeted drug deliveryIn vivoBiotinylationGliomaDrug DiscoveryGeneticsCancer researchmedicineMolecular MedicineMolecular imagingMolecular BiologyGenetics (clinical)The Journal of Gene Medicine
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On Transition Structures for Hydride Transfer Step: A Theoretical Study of the Reaction Catalyzed by Dihydrofolate Reductase Enzyme

1996

Abstract A theoretical study is presented of the catalytic mechanism of dihydrofolate reductase (DHFR) enzyme based upon the characterization of the transition structure (TS) for the hydride transfer step. Analytical gradients at AM1 and PM3 semiempirical levels have been used to characterize the saddle point of index one (SPi-1) on global energy hypersurface for the hydride transfer in the active site of DHFR enzyme. The geometry, stereochemistry, electronic structure, and transition vector (TV) components associated to SPi-1 are qualitatively computational level independent. The TV amplitudes show primary and secondary isotope effects to be strongly coupled. The geometrical arrangement of…

biologyHydrideStereochemistryChemistryOrganic ChemistryActive siteElectronic structureBiochemistryEnzyme catalysisCatalysisCrystallographySaddle pointDrug DiscoveryDihydrofolate reductaseKinetic isotope effectbiology.proteinMolecular BiologyBioorganic Chemistry
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Ophiobolin Sesterterpenoids and Pyrrolidine Alkaloids from the Sponge-Derived Fungus Aspergillus ustus

2011

Chemical examination of the fungus Aspergillus ustus isolated from the Mediterranean sponge Suberites domuncula yielded the five new ophiobolin-type sesterterpenoids 1–5 and the two new pyrrolidine alkaloids 6 and 7, together with the known compound aurantiamine and cerebroside D. The structures of the new compounds were unambiguously elucidated on the basis of extensive spectroscopic-data analysis (1D- and 2D-NMR, MS, and UV) and comparison with literature data. All compounds were evaluated for their cytotoxicity against murine lymphoma cell line L5178Y.

biologyMurine lymphomaChemistryStereochemistryOrganic ChemistryFungusbiology.organism_classificationBiochemistryCatalysisCerebrosidePyrrolidineInorganic ChemistrySuberites domunculaSpongechemistry.chemical_compoundBiochemistryAspergillus ustusDrug DiscoveryPhysical and Theoretical ChemistryCytotoxicityHelvetica Chimica Acta
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Coumarin derivatives from Pedilanthus tithymaloides as inhibitors of conidial germination in Magnaporthe oryzae

2012

In a screening for inhibitors of infection-related morphogenesis in the rice blast fungus Magnaporthe oryzae, a series of 10 coumarin derivatives were isolated from Pedilanthus tithymaloides (Euphorbiaceae). Seven of these compounds turned out to be known while three represent previously unreported natural products. Their structures were established on the basis of spectroscopic data and X-ray crystallography. Nine out of 10 coumarin derivatives were found to inhibit conidial germination in the phytopathogenic fungus at low concentrations.

biologyPedilanthus tithymaloidesChemistryOrganic ChemistryEuphorbiaceaeFungusbiology.organism_classificationCoumarinBiochemistryMagnaporthe oryzaechemistry.chemical_compoundBiochemistryGerminationDrug Discoveryheterocyclic compoundsVolume concentrationTetrahedron Letters
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Anhydrobiosis in yeast: FT-IR spectroscopic studies of yeast grown under conditions of severe oxygen limitation

2014

Anhydrobiosis is a unique state of living organisms when metabolism is temporarily and reversibly delayed in response to the extreme desiccation of cells. The production of dry active preparations of yeast grown under anaerobic conditions is not currently possible because preparations are extremely sensitive to the dehydration procedure, though they could be very helpful in different biotechnological processes, including bioethanol production. To characterize mechanisms responsible for such sensitivity to the dehydration procedure, Fourier transform infrared spectroscopy was used to study the composition of aerobically grown yeast Saccharomyces cerevisiae resistant to dehydration and grown …

biologyProcess Chemistry and TechnologySaccharomyces cerevisiaeBiomedical Engineeringchemistry.chemical_elementBioengineeringGeneral MedicineMetabolismbiology.organism_classificationmedicine.diseaseApplied Microbiology and BiotechnologyOxygenYeastchemistryBiochemistryDrug DiscoveryNucleic acidmedicineMolecular MedicineDehydrationDesiccationCryptobiosisBiotechnologyBiotechnology and Applied Biochemistry
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Potential ATPase mimics by polyammonium macrocycles: Criteria for catalytic activity

1992

Abstract A series of polyammonium macrocycles, ranging in size from the 18-membered ring [18]aneN6 to the 36-membered [36]aneN12 were examined as potential ATPase mimics. The rates of hydrolysis of ATP were followed at pH 3.0 and 7.0 using 31P NMR and HPLC techniques. Stability constants as a function of degree of protonation, distribution curves for the ligands as a function of pH, and distribution curves for the mixed species of nucleotides, inorganic phosphate, and macrocycle were also determined. All of the macrocycles catalyzed the hydrolysis of ATP to some extent compared to noncatalyzed hydrolysis. A critical dependence on macrocyclic ring size was observed, with [21]aneN7 being the …

biologyStereochemistryATPaseOrganic ChemistryProtonationCrystal structureRing (chemistry)PhosphateBiochemistryRing sizeHydrolysisCrystallographychemistry.chemical_compoundchemistryATP hydrolysisDrug Discoverybiology.proteinMolecular BiologyBioorganic Chemistry
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