Search results for "Cytotoxic"

showing 10 items of 1673 documents

Steroidal saponins from Raphia vinifera and their cytotoxic activity

2020

Abstract Phytochemical analysis of the fruits of Raphia vinifera led to the isolation of four new steroidal saponins (1–4), along with six known secondary metabolites (6–10). The structures of the isolated compounds were determined based on the analyses of NMR and mass spectrometric data, and chemical degradation reactions. Among the compounds tested, 1 and 4 showed the most promising cytotoxic activity against the drug-sensitive CCRF-CEM leukemia cell lines, with IC50 values of 3.55 µM and 7.14 µM, respectively.

Models MolecularClinical BiochemistryMolecular ConformationAntineoplastic Agents030209 endocrinology & metabolismArecaceaeBiochemistryLeukemia cell line03 medical and health sciences0302 clinical medicineEndocrinologyCell Line TumorIc50 valuesHumansCytotoxic T cellCytotoxicityMolecular BiologyPharmacologybiologyChemistryOrganic ChemistrySaponinsbiology.organism_classificationMass spectrometricRaphia viniferaPhytochemicalBiochemistry030220 oncology & carcinogenesisSteroidsSteroids
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Design, synthesis, and SAR analysis of cytotoxic sinapyl alcohol derivatives.

2005

Five series totalling 51 of sinapyl alcohol derivatives were designed and synthesized. Their cytotoxicity analyses were performed oil six human tumor cell lines Such as PC-3. CNE, KB, A549, BEL-7404, and HeLa. Certain sinapyl alcohol derivatives showed significant cytotoxic activities. Compound 14d exhibited especially potent cytotoxicity against the BEL-7404 cell line with an IC50 value of 0.7 mu M, which showed more cytotoxic activity than the positive control, cisplatin. The structure-cytotoxicity relationships were discussed and the CoMFA analysis was performed using the cytotoxic data against HeLa cells as a template. (c) 2005 Elsevier Ltd. All rights reserved.

Models MolecularClinical BiochemistryPharmaceutical ScienceQuantitative Structure-Activity RelationshipAntineoplastic AgentsBiochemistryChemical synthesisHeLachemistry.chemical_compoundInhibitory Concentration 50Cell Line TumorDrug DiscoveryElectrochemistryCytotoxic T cellHumansCytotoxicityMolecular BiologyIC50biologyPhenylpropionatesOrganic Chemistrybiology.organism_classificationIn vitroSinapyl alcoholchemistryBiochemistryCell cultureDrug DesignMolecular MedicineDrug Screening Assays AntitumorHeLa CellsBioorganicmedicinal chemistry
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Inhibitors of inducible NO synthase expression: total synthesis of (S)-curvularin and its ring homologues.

2008

(S)-Curvularin and its 13-, 14-, and 16-membered lactone homologues were synthesized through a uniform strategy in which a Kochi oxidative decarboxylation and ring-closing metathesis reactions constitute the key processes. In the evaluation of the anti-inflammatory effects of the synthesized compounds in assays using cells stably transfected with a human iNOS promoter-luciferase reporter gene construct, the 14- and 16-membered homologues showed a slightly higher inhibitory effect towards iNOS promoter activity than curvularin itself. However, the larger ring homologues also exhibited higher cytotoxicity, manifest in downregulated eNOS promoter activity. In contrast, the di-O-acetyl and 4-ch…

Models MolecularDrug Evaluation PreclinicalNitric Oxide Synthase Type IICrystallography X-RayBiochemistryGene Expression Regulation EnzymologicCell LineLactonesEnosDrug DiscoveryHumansGeneral Pharmacology Toxicology and PharmaceuticsEnzyme InhibitorsCytotoxicityPromoter Regions GeneticOxidative decarboxylationPharmacologychemistry.chemical_classificationReporter genebiologyMolecular StructureChemistryOrganic ChemistryTotal synthesisStereoisomerismCurvularinTransfectionbiology.organism_classificationBiochemistryCyclizationMolecular MedicineZearalenoneLactoneHeLa CellsChemMedChem
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In vitro leishmanicidal activity of pyrazole-containing polyamine macrocycles which inhibit the Fe-SOD enzyme of Leishmania infantum and Leishmania b…

2014

The in vitro leishmanicidal activity and cytotoxicity of pyrazole-containing macrocyclic polyamines 1-4 was assayed on Leishmania infantum and Leishmania braziliensis species. Compounds 1-4 were more active and less toxic than glucantime and both infection rates and ultrastructural alterations confirmed that 1 and 2 were highly leishmanicidal and induced extensive parasite cell damage. Modifications in the excretion products of parasites treated with 1-3 were also consistent with substantial cytoplasm alterations. Compound 2 was highlighted as a potent inhibitor of Fe-SOD in both species, whereas its effect on human CuZn-SOD was poor. Molecular modelling suggested that 2 could deactivate Fe…

Models MolecularLeishmanicidal activityErythrocytesMacrocyclic CompoundsAntioxidantCell Survivalmedicine.medical_treatmentAntiprotozoal AgentsProtozoan ProteinsBiologyLeishmania braziliensisCell LinePolyamine macrocyclechemistry.chemical_compoundMicroscopy Electron TransmissionIron superoxide dismutasePolyaminesmedicineAnimalsHumansLeishmania infantumCytotoxicityLeishmaniasischemistry.chemical_classificationMice Inbred BALB CSuperoxide DismutaseMacrophagesbiology.organism_classificationLeishmania braziliensisIn vitroInfectious DiseasesEnzymechemistryBiochemistryCell culturePyrazolePyrazolesFemaleAnimal Science and ZoologyParasitologyLeishmania infantumPolyamineParasitology
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Polyketide Derivatives from Mangrove Derived Endophytic Fungus Pseudopestalotiopsis theae

2020

Chemical investigation of secondary metabolites from the endophytic fungus Pseudopestalotiopsis theae led to the isolation of eighteen new polyketide derivatives, pestalotheols I&ndash

Models MolecularMagnetic Resonance SpectroscopyStereochemistryPharmaceutical Science010402 general chemistry01 natural sciencesArticlePolyketidepolyketideDrug DiscoverymedicineEndophytesCytotoxicityPharmacology Toxicology and Pharmaceutics (miscellaneous)IC50lcsh:QH301-705.5endophytic fungusbiologyMolecular Structure010405 organic chemistryChemistryAbsolute configurationFungibiology.organism_classification0104 chemical sciencesAcinetobacter baumanniiPseudopestalotiopsis theaelcsh:Biology (General)<i>Pseudopestalotiopsis theae</i>PolyketidesFermentationColistincytotoxicityRhizophoraceaeAntibacterial activityTwo-dimensional nuclear magnetic resonance spectroscopymedicine.drugMarine Drugs
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Dopaminergic isoquinolines with hexahydrocyclopenta[ ij ]-isoquinolines as D 2 -like selective ligands

2016

Dopamine receptors (DR) ligands are potential drug candidates for treating neurological disorders including schizophrenia or Parkinson's disease. Three series of isoquinolines: (E)-1-styryl-1,2,3,4-tetrahydroisoquinolines (series 1), 7-phenyl-1,2,3,7,8,8a-hexahydrocyclopenta[ij]-IQs (HCPIQs) (series 2) and (E)-1-(prop-1-en-1-yl)-1,2,3,4- tetrahydroisoquinolines (series 3), were prepared to determine their affinity for both D1and D2-like DR. The effect of different substituents on the nitrogen atom (methyl or allyl), the dioxygenated function (methoxyl or catechol), the substituent at the β-position of the THIQ skeleton, and the presence or absence of the cyclopentane motif, were studied. We…

Models MolecularMolecular modelProtein ConformationStereochemistryDopamine AgentsSubstituentCyclopentanesLigands010402 general chemistry01 natural sciencesSubstrate SpecificityStructure-Activity Relationshipchemistry.chemical_compoundDrug DiscoveryHuman Umbilical Vein Endothelial CellsmedicineHumansStructure–activity relationshipCYTOTOXICITYMOLECULAR MODELINGCyclopentaneSTRUCTURE-ACTIVITY RELATIONSHIPSTETRAHYDROISOQUINOLINESPharmacologyCatecholReceptors Dopamine D2010405 organic chemistryOtras Ciencias QuímicasOrganic ChemistryDopaminergicCiencias QuímicasGeneral MedicineIsoquinolines0104 chemical sciencesOxygenDOPAMINERGICchemistryTHIQHEXAHYDROCYCLOPENTAISOQUINOLINESSelectivityCIENCIAS NATURALES Y EXACTASmedicine.drugEuropean Journal of Medicinal Chemistry
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Triphenylphosphane Pt(II) complexes containing biologically active natural polyphenols: Synthesis, crystal structure, molecular modeling and cytotoxi…

2016

Platinum complexes bearing phosphane ligands in cis configuration with deprotonated flavonoids (3-hydroxyflavone, quercetin) and deprotonated ethyl gallate were synthesized starting from cis-[PtCl2(PPh3)(2)]. In all cases, O,O' chelate structures were obtained. While quercetin and ethyl gallate complexes are quite stable in solution, the 3-hydroxyflavonate complex undergoes a slow aerobic photodegradation in solution with formation of salicylic and benzoic acids. The X-ray diffraction structures of quercetin and ethyl gallate complexes are reported. Cell cycle studies (in the dark) of the complexes in two human cell lines revealed that the cytotoxic activity of the complex bearing 3-hydroxy…

Models MolecularPlatinum(II) complexesOrganoplatinum CompoundsMolecular modelStereochemistryPlatinum(II) complexes; Cytotoxic activity; Natural polyphenols; Flavonoids; DFTEthyl gallateCrystal structureCytotoxic activity; DFT; Flavonoids; Natural polyphenols; Platinum(II) complexesCrystallography X-Ray010402 general chemistry01 natural sciencesBiochemistryMedicinal chemistryDFTInorganic ChemistryHydrolysischemistry.chemical_compoundDeprotonationHumansChelationPhotodegradationCytotoxic activity DFT Flavonoids Natural polyphenols Platinum(II) complexesFlavonoidsCytotoxic activityCytotoxins010405 organic chemistryChemistryPolyphenols0104 chemical sciencesMCF-7 CellsNatural polyphenolsCis–trans isomerism
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Double-Network-Structured Graphene Oxide-Containing Nanogels as Photothermal Agents for the Treatment of Colorectal Cancer.

2017

Here, we reported the production of hyaluronic acid/polyaspartamide-based double-network nanogels for the potential treatment of colorectal carcinoma. Graphene oxide, thanks to the huge aromatic surface area, allows to easily load high amount of irinotecan (33.0% w/w) and confers to the system hyperthermic properties when irradiated with a near-infrared (NIR) laser beam. We demonstrate that the release of antitumor drug is influenced both by the pH of the external medium and the NIR irradiation process. In vitro biological studies, conducted on human colon cancer cells (HCT 116), revealed that nanogels are uptaken by the cancer cells and, in the presence of the antitumor drug, can produce a…

Models MolecularPolymers and PlasticsColorectal cancerInfrared RaysProtein ConformationNanogelsBioengineeringNanotechnologyAntineoplastic Agents02 engineering and technology010402 general chemistry01 natural scienceslaw.inventionPolyethylene GlycolsBiomaterialschemistry.chemical_compoundgraphene oxide hydrogel nenogel cancer therapylawHyaluronic acidMaterials ChemistrymedicineCytotoxic T cellHumansPolyethyleneimineHyaluronic AcidGrapheneChemistryOxidesPhotothermal therapy021001 nanoscience & nanotechnologymedicine.diseaseHCT116 CellsIn vitro0104 chemical sciencesIrinotecanPhotochemotherapyCancer cellCancer researchGraphite0210 nano-technologyColorectal Neoplasmsmedicine.drugBiomacromolecules
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2NH and 3OH are crucial structural requirements in sphingomyelin for sticholysin II binding and pore formation in bilayer membranes.

2013

AbstractSticholysin II (StnII) is a pore-forming toxin from the sea anemone Stichodactyla heliantus which belongs to the large actinoporin family. The toxin binds to sphingomyelin (SM) containing membranes, and shows high binding specificity for this lipid. In this study, we have examined the role of the hydrogen bonding groups of the SM long-chain base (i.e., the 2NH and the 3OH) for StnII recognition. We prepared methylated SM-analogs which had reduced hydrogen bonding capability from 2NH and 3OH. Both surface plasmon resonance experiments, and isothermal titration calorimetry measurements indicated that StnII failed to bind to bilayers containing methylated SM-analogs, whereas clear bind…

Models MolecularPore Forming Cytotoxic ProteinsMembrane permeabilizationLipid BilayersBiophysicsCalorimetryta3111Biochemistrychemistry.chemical_compoundCnidarian VenomsAnimalsComputer SimulationLipid bilayerta116Binding selectivityUnilamellar LiposomesPhosphocholineBinding SitesMolecular StructureChemistryHydrogen bondVesicleta1182Isothermal titration calorimetryHydrogen BondingCell BiologySurface Plasmon ResonanceProtein Structure TertiarySphingomyelinsKineticsMembraneSea AnemonesBiochemistryMolecular dockingIsothermal titration calorimetryBiophysicsPhosphatidylcholinesSphingomyelinProtein BindingBiochimica et biophysica acta
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Pore formation by Vibrio cholerae cytolysin follows the same archetypical mode as beta-barrel toxins from gram-positive organisms.

2009

Vibrio cholerae cytolysin (VCC) forms SDS-stable heptameric beta-barrel transmembrane pores in mammalian cell membranes. In contrast to structurally related pore formers of gram-positive organisms, no oligomeric prepore stage of assembly has been detected to date. In the present study, disulfide bonds were engineered to tie the pore-forming amino acid sequence to adjacent domains. In their nonreduced form, mutants were able to bind to rabbit erythrocytes and to native erythrocyte membranes suspended in PBS solution and form SDS-labile oligomers. These remained nonfunctional and represented the long-sought VCC prepores. Disulfide bond reduction in these oligomers released the pore-forming se…

Models MolecularPore Forming Cytotoxic ProteinsMutantBiologyIn Vitro Techniquesmedicine.disease_causeGram-Positive BacteriaBiochemistryModels Biologicalchemistry.chemical_compoundProtein structureGeneticsmedicineAnimalsCysteineProtein Structure QuaternaryMolecular BiologyPeptide sequenceVibrio choleraeCytotoxinsErythrocyte MembraneTransmembrane proteinRecombinant ProteinsMonomerMembraneBiochemistrychemistryVibrio choleraeMutagenesis Site-DirectedCytolysinRabbitsBiotechnologyFASEB journal : official publication of the Federation of American Societies for Experimental Biology
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