Search results for "Diazole"

showing 10 items of 263 documents

Evidence for a role of inducible nitric oxide synthase in gastric relaxation of mdx mice

2006

Alterations of gastric mechanical activity have been reported in mdx mouse, animal model for Duchenne muscular dystrophy. This study examined if alterations in the vasoactive intestinal polypeptide (VIP) system are present in mdx stomach. Gastric mechanical activity was recorded in vitro as changes of endoluminal pressure and neurally or pharmacologically evoked relaxations were analysed in mdxvs normal stomach. Reverse-transcription polymerase chain reaction was used to detect inducible nitric oxide synthase (iNOS) expression. Relaxations to sodium nitroprusside in mdx stomach showed no difference in comparison with normal preparations. In normal stomach, VIP produced relaxation, which was…

Malemedicine.medical_specialtymdx mousePhysiologyMuscle RelaxationVasoactive intestinal peptideNitric Oxide Synthase Type IIStimulationDUCHENNES MUSCULAR-DYSTROPHYSettore BIO/09 - FisiologiaNitric oxidechemistry.chemical_compoundMiceOrgan Culture TechniquesInternal medicineQuinoxalinesmedicineAnimalsRNA MessengerEnzyme InhibitorsReceptorOxadiazolesbiologyEndocrine and Autonomic SystemsReverse Transcriptase Polymerase Chain ReactionStomachStomachGastroenterologySMOOTH-MUSCLE CELLSMuscle SmoothPEPTIDE RELEASENitric oxide synthaseMuscular Dystrophy DuchenneDisease Models AnimalEndocrinologymedicine.anatomical_structureNG-Nitroarginine Methyl Esterchemistrybiology.proteinMice Inbred mdxReceptors Vasoactive Intestinal PeptideSodium nitroprussideIminesmedicine.drugVasoactive Intestinal Peptide
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Electron Ionization Induced Fragmentation of some 3-Aroylamino-5-Methyl-1,2,4- Oxadiazoles and 3-Acetylamino-5-Aryl-1,2,4-Oxadiazoles

2017

: Background and objectives. 1,2,4-Oxadiazoles show a high reactivity and represent starting compounds for the synthesis of several other heterocycles. Some their derivatives can give the so called Boulton-Katritzky Reactions (BKR) which opens the way to the synthesis of several azoles. For this reason we have registered the mass spectra of several 3-aroylamino-5-methyl-1,2,4-oxadiazoles and 3-acetylamino-5-aryl-1,2,4-oxadiazoles. Methods and results. Thus, studying the mass spectra of the isomeric couple 3-benzoylamino-5-methyl-1,2,4-oxadiazole (1A) and 3-acetylamino-5-phenyl-1,2,4-oxadiazoles (1B) we have observed that MIKE and CID MIKE spectra of their molecular ions and of the [M – CH2C…

Mass spectrometryStereochemistryArylOrganic ChemistryMass spectrometryPhotochemistrychemistry.chemical_compoundEI induced rearrangementchemistryFragmentation (mass spectrometry)Boulton-Katritzky Reactions (BKR)Fragmentation mechanism3-Acylamino-124-oxadiazolesElectron ionization
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New Imidazo[2,1-b][1,3,4]Thiadiazole Derivatives Inhibit FAK Phosphorylation and Potentiate the Antiproliferative Effects of Gemcitabine Through Modu…

2020

Background/aim A new class of imidazo[2,1-b][1,3,4]thiadiazole compounds have recently been evaluated as inhibitors of phosphorylation of focal adhesion kinase (FAK) in pancreatic cancer. FAK is overexpressed in mesothelioma and has recently emerged as an interesting target for the treatment of this disease. Materials and methods Ten imidazo[2,1-b][1,3,4]thiadiazole compounds characterized by indole bicycle and a thiophene ring, were evaluated for their cytotoxic activity in two primary cell cultures of peritoneal mesothelioma, MesoII and STO cells. Results Compounds 1a and 1b showed promising antitumor activity with IC50 values in the range of 0.59 to 2.81 μM in both cell lines growing as …

MesotheliomaCancer ResearchFAKbiologyChemistrygemcitabineSettore BIO/05 - Zoologiaimidazo[21-b][134]thiadiazole compoundGeneral MedicineEquilibrative nucleoside transporter 1medicine.diseaseSettore CHIM/08 - Chimica FarmaceuticaGemcitabineFocal adhesionOncologyCell culturePancreatic cancerbiology.proteinmedicineCancer researchPhosphorylationCytotoxic T cellhuman equilibrative nucleoside transporter-1.Nucleosidemedicine.drugAnticancer Research
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New linezolid-like 1,2,4-oxadiazoles active against Gram-positive multiresistant pathogens

2013

The synthesis and the in vitro antibacterial activity of novel linezolid-like oxadiazoles are reported. Replacement of the linezolid morpholine C-ring with 1,2,4-oxadiazole results in an antibacterial activity against Staphylococcus aureus both methicillin-susceptible and methicillin-resistant comparable or even superior to that of linezolid. While acetamidomethyl or thioacetoamidomethyl moieties in the C(5) side-chain are required, fluorination of the phenyl B ring exhibits a slight effect on an antibacterial activity but its presence seems to reduce the compounds cytotoxicity. Molecular modeling performed using two different approaches - FLAP and Amber software - shows that in the binding…

Methicillin-Resistant Staphylococcus aureusModels MolecularCell viabilityStaphylococcus aureusMolecular modelCell SurvivalMicrobial Sensitivity TestsAntimicrobial activityCrystallography X-Raymedicine.disease_causeDrug designMicrobiologyStructure-Activity Relationshipchemistry.chemical_compoundoxadiazoles linezolid antibioticsCell Line TumorDrug Resistance Multiple BacterialMorpholineAcetamidesDrug DiscoverymedicineHumansMoietyStructure–activity relationshipOxazolidinonesPharmacologyOxadiazolesOxazolidinones; Linezolid; Drug designDose-Response Relationship DrugMolecular StructureChemistryOrganic ChemistryLinezolidSettore CHIM/06 - Chimica OrganicaHep G2 CellsGeneral Medicinebiochemical phenomena metabolism and nutritionbacterial infections and mycosesSettore CHIM/08 - Chimica FarmaceuticaMethicillin-resistant Staphylococcus aureusCombinatorial chemistryOxazolidinoneAnti-Bacterial AgentsStaphylococcus aureusMED/07 - MICROBIOLOGIA E MICROBIOLOGIA CLINICALinezolidAntimicrobial activity; Cell viability; Drug design; Oxazolidinones; Staphylococcus aureusAntibacterial activitySoftware
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On the reaction of some 5-polyfluoroaryl-1,2,4-oxadiazoles with methylhydrazine: synthesis of fluorinated indazoles

2009

The reaction of 5-polyfluoroaryl-1,2,4-oxadiazoles with methylhydrazine has been studied and the synthesis of fluorinated N-methylindazoles has been realized. Rearrangement reactions showed predominantly formation of N(1)-methylindazole regioisomers. Starting compounds were preliminarily functionalized at the polyfluoroaryl moiety through fluorine displacement with nucleophiles (methanol, methylamine, dimethylamine), allowing the obtainment of target indazoles substituted at the C(6) position.

MethylhydrazineIndazoleMethylamineOrganic ChemistrySettore CHIM/06 - Chimica OrganicaBiochemistryMedicinal chemistryChemical synthesischemistry.chemical_compoundchemistryNucleophileDrug DiscoveryStructural isomerMoietyOrganic chemistryDimethylamine124-Oxadiazole Indazole Rearrangements Fluorinated heterocycles
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Synthesis, characterization, cellular uptake and interaction with native DNA of a bis(pyridyl)-1,2,4-oxadiazole copper(II) complex

2010

The copper(II) complex of 3,5-bis(2'-pyridyl)-1,2,4-oxadiazole was synthesized and characterized. X-Ray crystallography revealed that the complex consists of a discrete [Cu(3,5-bis(2'-pyridyl)-1,2,4-oxadiazole)(2)(H(2)O)(2)](2+) cation and two ClO(4)(-) anions. The Cu(II) coordination sphere has a distorted octahedral geometry and each ligand chelates the copper ion through the N(4) nitrogen of the oxadiazole ring and the nitrogen of one pyridine moiety. The coordinated water molecules are in cis position and each of them is H-bonded to the 5-pyridyl nitrogen of the oxadiazole ligand and to an oxygen of the perchlorate anion. Biological assays showed that, despite the free ligand not being …

Models MolecularCircular dichroismCoordination sphereheterocylces metal complex DNA binders anti-tumoralsCell SurvivalPyridinesStereochemistrychemistry.chemical_elementOxadiazoleLigandsInorganic Chemistrychemistry.chemical_compoundPerchlorateCell Line TumorOctahedral molecular geometryOrganometallic CompoundsHumansOxadiazolesChemistryLigandDNASettore CHIM/06 - Chimica OrganicaCopperBinding constantCrystallographySettore CHIM/03 - Chimica Generale E InorganicaCopper
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DNA binding and antiproliferative activity toward human carcinoma cells of copper(ii) and zinc(ii) complexes of a 2,5-diphenyl[1,3,4]oxadiazole deriv…

2012

The interaction of calf thymus DNA with [CuL(ClO(4))]ClO(4)·H(2)O (1) and [ZnLBr]Br·H(2)O (2) (L = 9,12,15,18,27,28-hexaaza-29-oxatetracyclo[24.2.1.0(2,7).0(20,25)]enneicosa-2,4,6,20,22,24,26,28(1)-octaene) dicationic complexes in aqueous solution at neutral pH, was investigated by variable-temperature UV-vis absorption, circular dichroism and fluorescence spectroscopy. The values of the DNA-binding constants of these complexes, determined by competitive binding spectrofluorimetric titrations of ethidium bromide (EB)-DNA solutions, are (6.7 ± 0.5) × 10(6) M(-1) for CuL(2+) and (4.7 ± 0.5) × 10(5) M(-1) for ZnL(2+). These data together with a through analysis of the spectroscopic behaviour c…

Models MolecularCircular dichroismDNA binding antiproliferative activity 25-diphenyl[134]oxadiazole derivativeStereochemistryCell SurvivalOxadiazoleAntineoplastic AgentsBreast NeoplasmsNucleic Acid DenaturationFluorescence spectroscopyInorganic Chemistrychemistry.chemical_compoundCoordination ComplexesCell Line TumorHumansOxazolesAqueous solutionDNAIn vitroZincchemistrySettore CHIM/03 - Chimica Generale E InorganicaTitrationFemaleEthidium bromideDNACopper
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1,2,4-Oxadiazole Topsentin Analogs with Antiproliferative Activity against Pancreatic Cancer Cells, Targeting GSK3β Kinase.

2021

A new series of topsentin analogs, in which the central imidazole ring of the natural lead was replaced by a 1,2,4- oxadiazole moiety, was efficiently synthesized. All derivatives were pre-screened for antiproliferative activity against the National Cancer Institute (NCI-60) cell lines panel. The five most potent compounds were further investigated in various pancreatic ductal adenocarcinoma (PDAC) cell lines, including SUIT-2, Capan-1, and Panc-1 cells, eliciting EC50 values in the micromolar and sub-micromolar range, associated with significant reduction of cell migration. These remarkable results might be explained by the effects of these new topsentin analogues on epithelial-to-mesenchy…

Models MolecularIndoles124-oxadiazole topsentin analogs; GSK3β kinase; inhibition of migration; PDAC antiproliferative activity; proapoptotic activityApoptosisDrug Screening Assays01 natural sciencesBiochemistrychemistry.chemical_compound124-oxadiazole topsentin analogs; GSK3β kinase; PDAC antiproliferative activity; inhibition of migration; proapoptotic activity; Antineoplastic Agents; Apoptosis; Cell Proliferation; Cell Survival; Dose-Response Relationship Drug; Drug Screening Assays Antitumor; Glycogen Synthase Kinase 3 beta; Humans; Imidazoles; Indoles; Models Molecular; Molecular Structure; Oxadiazoles; Pancreatic Neoplasms; Protein Kinase Inhibitors; Structure-Activity Relationship; Tumor Cells CulturedModelsAnnexinDrug DiscoveryTumor Cells CulturedGSK3β kinaseGeneral Pharmacology Toxicology and Pharmaceutics4-oxadiazole topsentin analogsOxadiazolesCulturedMolecular StructureChemistryKinaseImidazolesCell migrationTumor Cellsinhibition of migrationMolecular MedicineDrugIntracellularPDAC antiproliferative activityproapoptotic activityCell Survival12Antineoplastic AgentsDose-Response RelationshipStructure-Activity RelationshipPancreatic cancermedicineHumansPropidium iodideProtein Kinase InhibitorsCell ProliferationPharmacologyGlycogen Synthase Kinase 3 betaDose-Response Relationship Drug010405 organic chemistryOrganic ChemistryMolecularAntitumormedicine.diseaseSettore CHIM/08 - Chimica FarmaceuticaMolecular biology0104 chemical sciencesPancreatic Neoplasms010404 medicinal & biomolecular chemistryApoptosisCell cultureDrug Screening Assays Antitumor124-oxadiazole topsentin analogChemMedChem
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Experimental and DFT Studies on Competitive Heterocyclic Rearrangements. 3. A Cascade Isoxazole−1,2,4-Oxadiazole−Oxazole Rearrangement

2008

The thermal rearrangements of 3-acylamino-5-methylisoxazoles 1 have been investigated under basic and neutral conditions and interpreted with the support of computational data. The density functional theory (DFT) study on the competitive routes available for the base-catalyzed thermal rearrangement of isoxazoles 1 showed that the Boulton-Katritzky (BK) rearrangement, producing the less stable 3-acetonyl-1,2,4-oxadiazoles 5, is a much more favored process than either the migration-nucleophilic attack-cyclization (MNAC) or the ring contraction-ring expansion (RCRE). In turn, an increase in reaction temperature will promote the MNAC of oxadiazoles 5, producing the more stable 2-acylaminooxazol…

Molecular StructureStereochemistryOrganic ChemistryTemperatureOxadiazoleStereoisomerismRing (chemistry)Turn (biochemistry)chemistry.chemical_compoundModels ChemicalchemistryCyclizationComputational chemistryCascadeComputer SimulationDensity functional theoryIsoxazoleOxazolesOxazoleCope rearrangementThe Journal of Organic Chemistry
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On the reactivity of nitrosoimidazoles with acids (the Cusmano–Ruccia reaction): a continuous source of new ring-into-ring interconversion

2014

Abstract An extension of the ‘Cusmano–Ruccia’ reaction is reported. 6-(4-chlorophenyl)-3-methyl-5-nitrosoimidazo[2,1- b ]oxazole by the action of hydrochloric acid gives 3-(4-chlorobenzoyl)-5-methyl-1,2,4-oxadiazole ( 13 ); presumably via ammonium ion, CO 2 and methanol elimination. The relevance of the nature of the atom of the B -ring linked to C-2 of the imidazole for the occurrence of the ring-into-ring interconversion has been once more confirmed.

Multi-step processesOrganic ChemistryHydrochloric acidSettore CHIM/06 - Chimica OrganicaRing (chemistry)BiochemistryMedicinal chemistryIonConsedensed nitrosoimidazoles ring-into-ring interconversion multi-step processes 3-acyl-124-oxadiazoleschemistry.chemical_compoundchemistryCondensed nitrosoimidazoleDrug DiscoveryImidazoleAmmoniumReactivity (chemistry)MethanolRing-into-ring interconversionOxazoleTetrahedron Letters
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