Search results for "Aporphine"

showing 10 items of 17 documents

Synthesis of New 8-Arylisoquinoline Derivatives by Application of Palladium-Catalyzed Suzuki Cross-Coupling Reactions.

2005

Abstract New 8-(het)aryltetrahydroisoquinolines ( 10–14 ), 8-aryltetrahydroisoquinolin-4-ols ( 15 , 16 ), and 8-phenylisoquinolin-4-ol ( 17 ), flexible analogues of aporphine, were synthesized in good yields using palladium-catalyzed Suzuki cross-coupling reactions from 8-bromotetrahydroisoquinolin-4-one ( 6 ) as a common intermediate. We also describe the synthesis of this novel intermediate through an easy and efficient method, which involved intramolecular Friedel–Crafts cyclization.

Organic Chemistrychemistry.chemical_elementGeneral MedicineBiochemistryCombinatorial chemistryCoupling reactionCatalysischemistry.chemical_compoundchemistryIntramolecular forceDrug DiscoveryOrganic chemistryAporphinePalladiumChemInform
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Reactive oxygen species (ROS) generation inhibited by aporphine and phenanthrene alkaloids semi-synthesized from natural boldine.

2004

Four phenanthrene and one aporphine alkaloids semi-synthesized from boldine were evaluated for their inhibitory effect on reactive oxygen species (ROS) generation. ROS generation by neutrophils stimulated with N-formyl-methionyl-leucyl-phenylalanine was inhibited in a concentration dependent manner. Alkaloids exerted similar inhibitory effect in the hypoxanthine-xanthine oxidase system than in stimulated neutrophils, which could be attributed to a direct ROS scavenging activity. None of the alkaloids assayed had any effect on xanthine oxidase activity. Therefore the synthesized alkaloids might constitute an alternative therapy in inflammation disorders in which ROS generation is involved.

AporphinesStereochemistryNeutrophilsInflammationcomplex mixtureschemistry.chemical_compoundRos scavengingAlkaloidsDrug DiscoverymedicineBoldineHumansheterocyclic compoundsAporphineInhibitory effectchemistry.chemical_classificationReactive oxygen speciesOxidase testDose-Response Relationship DrugChemistryorganic chemicalsGeneral ChemistryGeneral MedicinePhenanthrenePhenanthrenesBiochemistrymedicine.symptomReactive Oxygen SpeciesChemicalpharmaceutical bulletin
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Halogenated derivatives of boldine with high selectivity for alpha1A-adrenoceptors in rat cerebral cortex.

1999

The selectivity of 3-nitrosoboldine and different halogenated derivatives of boldine (3-bromoboldine, 3,8-dibromoboldine and 3-chloroboldine) for alpha1-adrenoceptor subtypes was studied by examining [3H]-prazosin competition binding in rat cerebral cortex. In the competition experiments [3H]-prazosin binding was inhibited completely by all the compounds tested. The inhibition curves displayed shallow slopes which could be subdivided into high and low affinity components. The relative order of affinity and selectivity for alpha1A-adrenoceptors was 3-bromoboldine = 3,8-dibromoboldine = 3-chloroboldineboldine3-nitrosoboldine. The competition curves for 3-bromoboldine remained shallow and biph…

Cerebral CortexAporphinesChemistryStereochemistryHigh selectivityGeneral MedicinePrazosinBinding CompetitiveGeneral Biochemistry Genetics and Molecular BiologyRatschemistry.chemical_compoundDiltiazemStructure-Activity Relationshipmedicine.anatomical_structureHalogensCerebral cortexα1a adrenoceptorReceptors Adrenergic alpha-1medicineBoldineAnimalsFemaleGeneral Pharmacology Toxicology and PharmaceuticsRats WistarLife sciences
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Vascular Activity of (-)-Anonaine, (-)-Roemerine and (-)-Pukateine, Three Natural 6a(R)-1,2-Methylenedioxyaporphines with Different Affinities for α1…

2004

We have studied the mechanism of action of three 6a( R)-1,2-methylenedioxyaporphines as vasorelaxant compounds. The alkaloids assayed showed different affinities for the three human cloned alpha (1)-adrenoceptor (AR) subtypes stably expressed in rat-1 fibroblasts, showing lower affinity for alpha(1B)-AR with regard to the alpha(1A)- or alpha(1D)-subtypes. These three natural compounds are more potent inhibitors of [ (3)H]-prazosin binding than of [ (3)H]-diltiazem binding to rat cerebral cortical membranes. As all these alkaloids inhibited noradrenaline (NA)-induced [ (3)H]-inositol phosphate formation in cerebral cortex and rat tail artery, they may be safely viewed as alpha (1)-AR antagon…

AporphinesPhosphodiesterase InhibitorsStereochemistryPharmaceutical ScienceAorta ThoracicDioxolesBiologyMuscle Smooth VascularAnalytical ChemistryHydroxylationchemistry.chemical_compoundAlkaloidsDrug DiscoverymedicineAnonaineAnimalsHumansAporphineRats WistarBinding sitePukateineCerebral CortexPharmacologyPlants MedicinalVoltage-dependent calcium channelAlkaloidOrganic ChemistryArteriesReceptors Adrenergic alphaIsoquinolinesRatsComplementary and alternative medicineMechanism of actionchemistryMolecular MedicineFemaleCalcium Channelsmedicine.symptomDrugs Chinese HerbalPhytotherapyPlanta Medica
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New alkaloid antibiotics that target the DNA topoisomerase I of Streptococcus pneumoniae

2011

16 pags, 3 figs, 3 tabs

Models MolecularTopoisomerase-I Inhibitormedicine.disease_causeMicrobiologyBiochemistryCell LineMicrobiology03 medical and health scienceschemistry.chemical_compoundAlkaloidsBacterial ProteinsStreptococcus pneumoniaemedicineHumansAporphineMolecular BiologyEscherichia coli030304 developmental biologychemistry.chemical_classification0303 health sciencesDose-Response Relationship Drugbiology030306 microbiologyTopoisomeraseCell BiologyPhenanthrenesProtein Structure TertiaryAnti-Bacterial Agents3. Good healthStreptococcus pneumoniaeEnzymeDNA Topoisomerases Type IchemistryBiochemistrybiology.proteinDNA supercoilTopoisomerase I InhibitorsGrowth inhibitionJournal of Biological Chemistry 286: 6402-6413 (2011)
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The 5-HT and alpha-adrenoceptor antagonist effect of four benzylisoquinoline alkaloids on rat aorta.

1998

Abstract The action of four benzylisoquinoline alkaloids (two aporphines—glaucine and apomorphine, a benzylisoquinoline—papaverine and a bisbenzyltetrahydroisoquinoline—antioquine) on 5-HT-induced contraction in rat thoracic aorta has been examined and compared with that of the control drugs: ketanserin, nifedipine, prazosin and phentolamine. The relaxant action on 5-HT-induced contraction was contrasted with that on the contraction induced by noradrenaline and KCl. The results obtained with control drugs show that ketanserin has clear selectivity for 5-HT receptors, whereas prazosin and phentolamine have high selectivity for the α1-adrenoceptor and nifedipine seems to have a more potent ef…

AgonistMalemedicine.medical_specialtySerotoninKetanserinAporphinesApomorphinemedicine.drug_classPharmaceutical ScienceAorta ThoracicIn Vitro TechniquesBenzylisoquinolinesMuscle Smooth Vascularchemistry.chemical_compoundPhentolamineAlkaloidsInternal medicinePapaverinemedicinePrazosinAnimalsRats WistarBenzylisoquinolineAdrenergic alpha-AntagonistsPharmacologyPapaverineDose-Response Relationship DrugChemistryParasympatholyticsCalcium Channel BlockersIsoquinolinesGlaucineRatsApomorphineEndocrinologyDopamine Agonistsmedicine.drugMuscle ContractionThe Journal of pharmacy and pharmacology
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3,4-Dihydroxy- and 3,4-methylenedioxy- phenanthrene-type alkaloids with high selectivity for D2 dopamine receptor.

2013

Abstract Dopamine-mediated neurotransmission plays an important role in relevant psychiatric and neurological disorders. Nowadays, there is an enormous interest in the development of new drugs acting at the dopamine receptors (DR) as potential new targets for the treatment of schizophrenia or Parkinson’s disease. Previous studies have revealed that isoquinoline compounds such as tetrahydroisoquinolines (THIQs) can behave as selective D 2 dopaminergic alkaloids. In the present study we have synthesized five aporphine compounds and five phenanthrene alkaloids and evaluated their potential dopaminergic activity. Binding studies on rat striatal membranes were used to evaluate their affinity and…

StereochemistryClinical BiochemistryPharmaceutical ScienceNeurotransmissionPharmacologyBiochemistryMethylenedioxychemistry.chemical_compoundAlkaloidsDrug DiscoveryAnimalsHumansAporphineIsoquinolineMolecular BiologyChemistryReceptors Dopamine D2Organic ChemistryDopaminergicParkinson DiseasePhenanthrenePhenanthrenesCorpus StriatumRatsDopamine receptorSchizophreniaMolecular MedicineSelectivityBioorganicmedicinal chemistry letters
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Effect of boldine, secoboldine, and boldine methine on angiotensin II-induced neutrophil recruitment in vivo.

2005

AbstractAngiotensin-II (Ang-II) has inflammatory activity and is involved in different diseases associated with the cardiovascular system. This study has evaluated the effect of boldine (B), and two phenanthrene alkaloids semisynthesized by us, secoboldine (SB) and boldine methine (BM), on Ang-II-induced neutrophil recruitment. Intraperitoneal administration of 1 nM Ang-II induced significant neutrophil accumulation, which was maximal at 4–8 h. BM inhibited neutrophil infiltration into the peritoneal cavity at 4 h and 8 h by 73% and 77%, respectively, SB at 8 h by 55%, and B had no effect on this response. Although BM inhibited the release of cytokine-inducible neutrophil chemoattractant/ke…

KeratinocytesMaleChemokineAporphinesEndotheliumNeutrophilsImmunologyChemokine CXCL2InflammationPharmacologyRats Sprague-Dawleychemistry.chemical_compoundIn vivomedicineImmunology and AllergyBoldineAnimalsHumansInfusions ParenteralPlatelet Activating FactorReceptorchemistry.chemical_classificationReactive oxygen speciesbiologyMolecular StructureAngiotensin IIMonokinesInterleukin-8Endothelial CellsCell BiologyPhenanthrenesAngiotensin IIRatsP-Selectinmedicine.anatomical_structureBiochemistrychemistrybiology.proteinIntercellular Signaling Peptides and Proteinsmedicine.symptomChemokinesReactive Oxygen SpeciesChemokines CXCJournal of leukocyte biology
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8-NH2-Boldine, an Antagonist of α1Aand α1BAdrenoceptors without Affinity for the α1DSubtype: Structural Requirements for Aporphines at α1-Adrenocepto…

2005

Structure-activity analysis of 21 aporphine derivatives was performed by examining their affinities for cloned human alpha (1A), alpha (1B) and alpha (1D) adrenoceptors (AR) using membranes prepared from rat-1 fibroblasts stably expressing each alpha (1)-AR subtype. All the compounds tested competed for [ (125)I]-HEAT binding with steep and monophasic curves. The most interesting compound was 8-NH (2)-boldine, which retains the selective affinity for alpha(1A)-AR (pKi = 6.37 +/- 0.21) vs. alpha(1B)-AR (pKi = 5.53 +/- 0.11) exhibited by 1,2,9,10-tetraoxygenated aporphines, but shows low affinity for alpha(1D)-AR (pKi < 2.5). Binding studies on native adrenoceptors present in rat cerebral cor…

Pharmacologychemistry.chemical_classificationeducation.field_of_studyAdrenergic receptorStereochemistryOrganic ChemistryPopulationAntagonistPharmaceutical ScienceBiologyAnalytical Chemistrychemistry.chemical_compoundComplementary and alternative medicinechemistryDrug DiscoveryMolecular MedicineStructure–activity relationshipBoldineAporphineBinding siteInositol phosphateeducationPlanta Medica
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Effects of inhaled glaucine on pulmonary responses to antigen in sensitized guinea pigs.

2000

The alkaloid (S)-(+)-1,2,9,10-tetramethoxyaporphine (glaucine) is a phosphodiesterase 4 inhibitor with bronchodilator and anti-inflammatory activity in vitro. In this study, we examined the in vivo effects of glaucine on an animal model of asthma. In ovalbumin sensitized guinea pigs, inhaled glaucine (10 mg ml(-1), 3 min) inhibited the acute bronchoconstriction produced by aerosol antigen (antigen response was 256+/-42 and 95+/-14 cm H(2)O l(-1) s(-1) in control and glaucine-treated animals, respectively; P<0.05). Pretreatment with glaucine (10 mg ml(-1), 10 min inhalation, 30 min pre- and 3 h post-antigen exposure) markedly reduced airway hyperreactivity to histamine, eosinophil lung accum…

MalePulmonary CirculationAporphinesEosinophil Peroxidasemedicine.drug_classBronchoconstrictionGuinea PigsPharmacologyGuinea pigCapillary Permeabilitychemistry.chemical_compoundBronchodilatormedicineCyclic AMPAnimalsAntigensLungPharmacologybiologyInhalationDose-Response Relationship Drugbusiness.industryrespiratory systemEosinophilGlaucineCyclic Nucleotide Phosphodiesterases Type 4EosinophilsTracheamedicine.anatomical_structurechemistryPeroxidases3'5'-Cyclic-AMP PhosphodiesterasesImmunologybiology.proteinBronchoconstrictionVascular Resistancemedicine.symptomBronchial HyperreactivitybusinessEosinophil peroxidaseHistamineHistamineEuropean journal of pharmacology
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