Search results for "VITRO"

showing 10 items of 2786 documents

Efficient synthesis and 5-LOX/COX-inhibitory activity of some 3-hydroxybenzo[b]thiophene-2-carboxylic acid derivatives

2012

Abstract A series of 3-hydroxybenzo[ b ]thiophene-2-carboxylic acid derivatives has been prepared and subsequently evaluated with regards to the inhibition of 5-LOX/COX. Structure optimization furnished derivatives with promising in vitro activity as dual 5-LOX/COX inhibitors with submicromolar IC 50 values for inhibition of 5-LOX and COX-1, respectively.

StereochemistryCarboxylic acidClinical BiochemistryCarboxylic AcidsPharmaceutical ScienceThiophenesInhibitory postsynaptic potentialBiochemistryStructure-Activity Relationshipchemistry.chemical_compoundDrug DiscoveryThiopheneCyclooxygenase InhibitorsLipoxygenase InhibitorsMolecular Biologychemistry.chemical_classificationArachidonate 5-Lipoxygenaseintegumentary systemOrganic Chemistryfood and beveragesBenzothiopheneIn vitrochemistryCyclooxygenase 1Molecular MedicineLicofeloneProtein BindingBioorganic & Medicinal Chemistry Letters
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Genotoxic and endocrine activities of bis(hydroxyphenyl)methane (bisphenol F) and its derivatives in the HepG2 cell line

2008

International audience; Human can be exposed to bis(hydroxyphenyl)methane (bisphenol F or BPF) and its derivatives as environment and food's contaminants. This study was investigated to identify and to compare toxic potency of BPF, BFDGE, and two of BPF metabolites using in vitro methods. BPF did not induce any genic mutation in bacteria when the Ames test was performed according to the OECD guideline. In contrast, using Human cell lines and Comet assay, we demonstrated that BPF and Bisphenol F Diglycidyl Ether (BFDGE) were effective on HepG2 cell DNA fragmentation at non-cytotoxic concentrations. DHB was also positive but at higher concentrations, near its limit of solubility. Neither BPF,…

StereochemistryCell SurvivalEndocrine activitiesOxidative BPF metabolitesBisphenol F Diglycidyl Ether (BFDGE)[SDV.TOX.TCA]Life Sciences [q-bio]/Toxicology/Toxicology and food chain010501 environmental sciencesEndocrine DisruptorsToxicologymedicine.disease_causeTransfection01 natural sciencesAmes testCell Line03 medical and health scienceschemistry.chemical_compoundHuman cell linesmedicineHumansEstrogens Non-SteroidalBenzhydryl CompoundsBisphenol F (BPF)Bisphenol A diglycidyl ether030304 developmental biology0105 earth and related environmental sciences0303 health sciencesMicronucleus TestsMutagenicity TestsAndrogen AntagonistsMolecular biologyIn vitro3. Good healthComet assaychemistryCell cultureMicronucleus testDNA fragmentationComet AssayGenotoxicityGenotoxicityMutagens
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Identification of a Terphenyl Derivative that Blocks the Cell Cycle in the G0−G1 Phase and Induces Differentiation in Leukemia Cells

2006

To further explore the SAR of resveratrol-related trans-stilbene derivatives, here we describe the synthesis of (a) a series of 3,5-dimethoxy analogues in which a variety of substituents were introduced at positions 2', 3', 4', and 5' of the stilbene scaffold and (b) a second group of derivatives (2-phenylnaphthalenes and terphenyls) that incorporate a phenyl ring as a bioisosteric replacement of the stilbene alkenyl bridge. We thoroughly characterized all of the new compounds with respect to their apoptosis-inducing activity and their effects on the cell cycle. One of the new derivatives, 13g, behaved differently from the others, as it was able to block the cell cycle in the G(0)-G(1) phas…

StereochemistryCellular differentiationFusion Proteins bcr-ablAntineoplastic AgentsApoptosis.ResveratrolResting Phase Cell CycleChemical synthesisStructure-Activity Relationshipchemistry.chemical_compoundLeukemia Promyelocytic AcuteCell Line TumorTerphenyl CompoundsTerphenylStilbenesDrug DiscoveryHumansStructure–activity relationshipATP Binding Cassette Transporter Subfamily B Member 1G1 PhaseCell DifferentiationCell cycleIn vitrochemistryDrug Resistance NeoplasmResveratrolCell cultureMolecular MedicineDrug Screening Assays AntitumorJournal of Medicinal Chemistry
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In vivo and in vitro anti-leishmanial activities of 4-nitro-N-pyrimidin- and N-pyrazin-2-ylbenzenesulfonamides, and N2-(4-nitrophenyl)-N1-propylglyci…

2009

A series of compounds containing the nitrobenzene and sulfonamido moieties were synthesized and their leishmanicidal effect was assessed in vitro against Leishmania infantum promastigotes. Among the compounds evaluated, the p-nitrobenzenesulfonamides 4Aa and 4Ba, and the p-nitroaniline 5 showed significant activity with a good selectivity index. In a Balb/c mice model of L. Infantum, administration of compounds 4Aa, 4Ba or 5 (5 mg/kg/day for 10 days, injected ip route) led to a clear-cut parasite burden reduction (ca. 99%). In an attempt to elucidate their mechanism of action, the DNA interaction of 4Aa and 5 was investigated by means of viscosity studies, thermal denaturation and nuclease …

StereochemistryClinical BiochemistryNitro compoundGlycinePharmaceutical ScienceBiochemistryChemical synthesisMiceIn vivoDrug DiscoverymedicineAnimalsMolecular BiologyLeishmaniasischemistry.chemical_classificationNucleaseMice Inbred BALB CSulfonamidesAniline CompoundsbiologyOrganic Chemistrybiology.organism_classificationTrypanocidal AgentsIn vitroPyrimidineschemistryMechanism of actionBiochemistrybiology.proteinNitroMolecular MedicineLeishmania infantummedicine.symptomBioorganicmedicinal chemistry
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[68Ga]Ga-DO2A-(OBu-l-tyr)2: Synthesis, 68Ga-radiolabeling and in vitro studies of a novel 68Ga-DO2A-tyrosine conjugate as potential tumor tracer for …

2009

The synthesis, (68)Ga-labeling and in vitro study of the novel tyrosine chelate derivative [(68)Ga]Ga-1,4,7,10-tetraazacyclododecane-1,7-diacetic acid-4,10-di-(O-butyl)-l-tyrosine ([(68)Ga]Ga-DO(2)A-(OBu-l-tyr)(2)) as a potential tracer for imaging tumor metabolism by positron emission tomography (PET) is presented. This approach combines the biological amino acid transporter targeting properties of l-tyrosine with the outstanding availability of (68)Ga(III) via the (68)Ge/(68)Ga generator. In vitro studies utilizing the F98-glioblastoma cell line revealed specific uptake of [(68)Ga]Ga-DO2A-(OBu-l-tyr)(2) that was comparable to that of the reference O-(2-[(18)F]fluoroethyl)-l-tyrosine (FET)…

StereochemistryClinical BiochemistryPharmaceutical ScienceBiochemistryChemical synthesisCell Line TumorDrug DiscoveryOrganometallic CompoundsAnimalsChelationAmino acid transporterTyrosineMolecular BiologyGallium IsotopesFluoroethylBrain NeoplasmsChemistryOrganic ChemistryLigand (biochemistry)In vitroRatsPositron-Emission TomographyMolecular MedicineRadiopharmaceuticalsGlioblastomaConjugateBioorganic & Medicinal Chemistry Letters
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Synthesis and cytotoxicity of 6,11-Dihydro-pyrido- and 6,11-Dihydro-benzo[2,3-b]phenazine-6,11-dione derivatives

2003

6,11-Dihydro-pyrido[2,3-b]phenazine-6,11-diones and 6,11-dihydro-benzo[2,3-b]phenazine-6,11-diones were synthesized from 6,7-dichloro-5,8-quinolinedione and 2,3-dichloro-1,4-naphthoquinone. The study on the cytotoxicity on these products revealed that the pyridophenazinediones, tetracyclic heteroquinone analogues with three nitrogen atoms exhibited a high cytotoxicity on several human tumor cell lines. Compound 9c and 9e showed in vitro antitumor activity comparable or superior to doxorubicin against the human ovarian tumor cells (SK-OV-3) and the human CNS cells (XF 498). The IC(50) value for compound 9e was 0.06 microM against the human CNS cells (XF 498), which was 2.6 times higher than …

StereochemistryClinical BiochemistryPhenazinePharmaceutical ScienceAntineoplastic AgentsCrystallography X-RayBiochemistryChemical synthesisInhibitory Concentration 50Structure-Activity Relationshipchemistry.chemical_compoundDrug DiscoveryTumor Cells CulturedNucleophilic substitutionHumansStructure–activity relationshipCytotoxicityMolecular BiologyMolecular StructureOrganic ChemistryIn vitroQuinonechemistryDoxorubicinCell cultureQuinolinesPhenazinesMolecular MedicineDrug Screening Assays AntitumorNaphthoquinonesBioorganic & Medicinal Chemistry
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Gamma-lactone-Functionalized antitumoral acetogenins are the most potent inhibitors of mitochondrial complex I.

2001

To study the relevance of the terminal alpha,beta-unsaturated gamma-methyl-gamma-lactone moiety of the antitumoral acetogenins of Annonaceae for potent mitochondrial complex I inhibition, we have prepared a series of semisynthetic acetogenins with modifications only in this part of the molecule, from the natural rolliniastatin-1 (1) and cherimolin-1 (2). Some of the hydroxylated derivatives (1b, 1d and 1e) in addition to two infrequent natural beta-hydroxy gamma-methyl gamma-lactone acetogenins, laherradurin (3) and itrabin (4), are more potent complex I inhibitors than any other known compounds.

StereochemistryClinical BiochemistrySubmitochondrial ParticlesPharmaceutical ScienceAntineoplastic AgentsMitochondrionBiochemistryMitochondria HeartLactonesMagnoliopsidaMultienzyme ComplexesDrug DiscoveryMoietyAnimalsNADH NADPH OxidoreductasesFuransMolecular Biologychemistry.chemical_classificationElectron Transport Complex IbiologyMolecular StructureOrganic ChemistryBiological activitybiology.organism_classificationIn vitroEnzymechemistryEnzyme inhibitorAnnonaceaebiology.proteinMolecular MedicineCattleLactoneBioorganicmedicinal chemistry letters
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Synthesis and in vitro antileukemic activity of new 4-triazenopyrazole derivatives

2003

Several new 4-(3,3-dimethyltriazeno)-5-benzamidopyrazole derivatives were prepared by reacting 4-diazo-5-benzamidopyrazole derivatives with dimethylamine. The compounds were tested at 10 microM for their vitro antileukemic activity against K562 (Human chronic myelogenous leukemia) and Raji (human Burkitt limphoma ) cell lines. Dacarbazine and methotrexate were used for comparative purpose. The 3-methyl-4-(3,3-dimethyltriazeno)-5-(substituted benzamido)pyrazoles, bearing the pyrazole nucleus free at 1 position, resulted more active than the 1-(substituted phenyl)-3-methyl-4-(3,3-dimethyltriazeno)-5-benzamidopyrazoles. Dacarbazine at 10 microM showed no activity in the above tests. The observ…

StereochemistryDacarbazinePharmaceutical ScienceAntineoplastic AgentsPyrazoleSettore BIO/19 - Microbiologia GeneraleInhibitory Concentration 50Structure-Activity Relationshipchemistry.chemical_compoundCytochrome P-450 Enzyme SystemCell Line TumorLeukemia Myelogenous Chronic BCR-ABL PositiveDrug DiscoverymedicineHumansDimethylamine4-Triazenopyrazoles Antiproliferative activity In vitro antileukemic acitivityDemethylationTriazinesGeneral MedicineBurkitt LymphomaSettore CHIM/08 - Chimica FarmaceuticaIn vitroRaji cellchemistryMechanism of actionPyrazolesGrowth inhibitionmedicine.symptommedicine.drugIl Farmaco
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Synthesis and pharmacology of 6-substituted benztropines: discovery of novel dopamine uptake inhibitors possessing low binding affinity to the dopami…

2005

A series of 6alpha- and 6beta-substituted benztropines were synthesized. A marked enantioselectivity was observed for the 6beta-methoxylated benztropines, the (1R)-isomers being more potent than the corresponding (1S) compounds. The racemic 6alpha-methoxy-3-(4',4' '-difluorodiphenylmethoxy)tropane (5 g) was the most potent compound. It has been found that modifications at the 6-position of benztropine might reduce the DAT binding affinity, maintaining otherwise a significant dopamine uptake inhibitory activity. A reinvestigation of the absolute configuration of 6beta-methoxytropinone proved the 6R configuration for the (+)-enantiomer.

StereochemistryDopamineDopamine Plasma Membrane Transport ProteinsMolecular ConformationNerve Tissue ProteinsIn Vitro TechniquesBinding CompetitiveDopamine Plasma Membrane Transport ProteinRadioligand AssayStructure-Activity Relationshipchemistry.chemical_compoundDopamine Uptake InhibitorsCocaineDopaminetriple reuptakeDrug DiscoveryDopamine Uptake InhibitorsmedicineAnimalsStructure–activity relationshipDopamine transporterBenztropineNerve EndingsDopamine Plasma Membrane Transport ProteinsMembrane GlycoproteinsbiologyPutamenMembrane Transport ProteinsStereoisomerismTropaneBiological activityCorpus StriatumBenztropineRatschemistrybiology.proteinMolecular MedicineTropanesmedicine.drug
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Pyrrolo[2,3-h]quinolinones: synthesis and photochemotherapic activity.

2003

A series of derivatives of the new ring system pyrrolo[2,3-h]quinoline-2-one was synthesized and evaluated as photoreagents toward cultured human tumor cells. Remarkable phototoxycity resulted for some derivatives, especially those bearing the phenyl group at the 7-position.

StereochemistryFibrosarcomaClinical BiochemistryPharmaceutical ScienceAntineoplastic AgentsQuinolonesRing (chemistry)BiochemistryChemical synthesischemistry.chemical_compoundStructure-Activity RelationshipDrug DiscoveryTumor Cells CulturedPhenyl groupHumansPhotosensitizerPyrrolesMolecular BiologyPhotosensitizing AgentsChemistryOrganic ChemistryGeneral MedicineIn vitroHuman tumorPhotochemotherapyCell cultureLactamMolecular MedicineDrug Screening Assays AntitumorBioorganicmedicinal chemistry letters
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