Search results for "Cytotoxic"

showing 10 items of 1673 documents

New complex polycyclic compounds: Synthesis, antiproliferative activity and mechanism of action

2020

Abstract Polycyclic or O-glycoconiugate polycyclic compounds 1a-g were previously tested for their in vitro antiproliferative activity. In this series of compounds, activity increases as log P decreases. Specifically, compounds 1d and 1g showed lower log P values together with the best antiproliferative profiles. With the aim of extending our understanding of the structure–activity relationship (SAR) of this class of compounds, we prepared new polycyclic derivatives 2a-c, which bear on each of the two phenyl rings hydrophilic substituents (OH, SO2NH2 or NHCOCH3). These substituents are able to form hydrogen bonds and to decrease the partition coefficient value as compared with compound 1d. …

StereochemistryO-glycoconjugate polycyclic compoundsApoptosisAntiproliferative activityCrystallography X-Ray01 natural sciencesBiochemistryStructure-Activity RelationshipBreast cancer cell lineCell Line TumorDrug DiscoverymedicineAutophagyMDA-MB231 breast cancer cellsHumansPolycyclic CompoundsCytotoxicityMolecular BiologyCell Proliferation010405 organic chemistryHydrogen bondChemistryOrganic ChemistryHydrogen BondingIn vitro0104 chemical sciencesPartition coefficient010404 medicinal & biomolecular chemistryMechanism of actionApoptosisPyrazolo[34-b]pyrazolo[3′4′:23]azepino[45-f]azocinemedicine.symptom
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Phytochemical Profile and Apoptotic Activity of Onopordum cynarocephalum.

2012

A phytochemical investigation of acetone and chloroform extracts of the aerial parts of Onopordum cynarocephalum Boiss. et Blanche was carried out. It led to the isolation of two new sesquiterpenes, the elemane aldehyde (2) and the eudesmane (11), together with 15 known compounds: two lignans (1 and 15) and 13 sesquiterpenes (3–10, 12–14, 16, 17). The structures were elucidated by spectroscopic analyses, especially 1D and 2D NMR spectra. The anti-growth effect against three human melanoma cell lines, M14, A375, and A2058, of the different extracts and compounds of O. cynarocephalum was also investigated. Among them, the chloroform extract exhibited the strongest biological activity, while t…

StereochemistryPharmaceutical ScienceApoptosisDNA FragmentationLignansAnalytical Chemistrychemistry.chemical_compoundInhibitory Concentration 50cytotoxic activity Onopordum cynarocephalum Boiss. et BlancheCell Line TumorDrug DiscoveryHumansSesquiterpenes EudesmaneHSP70 Heat-Shock ProteinsFuransArctigeninCell ProliferationPharmacologyLignanChloroformPlants MedicinalbiologyDose-Response Relationship DrugMolecular StructureCaspase 3Plant ExtractsOrganic ChemistryOnopordumPTEN PhosphohydrolaseBiological activityPlant Components AerialAntineoplastic Agents PhytogenicEnzyme assayMonocyclic SesquiterpenesComplementary and alternative medicinePhytochemicalchemistryApoptosisbiology.proteinMolecular MedicineDNA fragmentationSesquiterpenes
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Cytotoxicity and modes of action of four naturally occuring benzophenones: 2,2′,5,6′-Tetrahydroxybenzophenone, guttiferone E, isogarcinol and isoxant…

2012

Abstract Introduction The emergence of drug-resistant cancer cells drastically reduces the efficacy of many antineoplasic agents and, consequently, increases the frequency of therapeutic failure. Benzophenones are known to display many pharmacological properties including cytotoxic activities. The present study was aimed at investigating the cytotoxicity and the modes of action of four naturally occurring benzophenones 2,2′,5,6′-tetrahydroxybenzophenone ( 1 ), isogarcinol ( 2 ), isoxanthochymol ( 3 ) and guttiferone E ( 4 ) on a panel of eleven cancer cell lines including various sensitive and drug-resistant phenotypes. Methods The cytotoxicity of the compounds was determined using a resazu…

StereochemistryPharmaceutical ScienceApoptosisHL-60 CellsPharmacologyCaspase 8BenzophenonesInhibitory Concentration 50NeoplasmsDrug DiscoveryHumansCytotoxic T cellCytotoxicityCaspaseCell ProliferationPharmacologyCaspase-9LeukemiabiologyPlant ExtractsChemistryCarcinomaHCT116 CellsAntineoplastic Agents PhytogenicMatrix MetalloproteinasesPhenotypeComplementary and alternative medicineDoxorubicinDrug Resistance NeoplasmApoptosisCell cultureCaspasesColonic NeoplasmsCancer cellbiology.proteinMolecular MedicineReactive Oxygen SpeciesPhytotherapyPhytomedicine
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Furoquinolines and dihydrooxazole alkaloids with cytotoxic activity from the stem bark of Araliopsis soyauxii.

2018

Abstract Two new furoquinoline alkaloids, maculine B (1) and kokusaginine B (2) and one new dihydrooxazole alkaloid, veprisazole (3), along with four known compounds namely, N13-methyl-3-methoxyrutaecarpine (4), flindersiamine (5), skimmianine (6) and tilianin (7) were isolated from the methanol extract of the stem bark of Araliopsis soyauxii Engl. by various chromatographic methods. Their structures were determined using spectrometry and spectroscopic techniques including NMR and MS. The cytotoxicity of the new compounds compared to that of doxorubicin, the reference anticancer compound, was determined on a panel of nine cancer cell lines including sensitive and drug resistant phenotypes. …

StereochemistryPhytochemicalsDioxoles01 natural sciencesAlkaloidsCell Line TumorDrug DiscoverymedicineCytotoxic T cellHumansDoxorubicinCameroonGlycosidesMedicinal plantsCytotoxicityFuransIC50RutaceaePharmacologyFlavonoidsMolecular Structure010405 organic chemistryChemistryAlkaloidGeneral MedicineAntineoplastic Agents PhytogenicDrug Resistance Multiple0104 chemical sciences010404 medicinal & biomolecular chemistryCell cultureDrug Resistance Neoplasmvisual_artvisual_art.visual_art_mediumPlant BarkQuinolinesBarkmedicine.drugFitoterapia
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Stereoselective synthesis and determination of the cytotoxic properties of spicigerolide and three of its stereoisomers.

2003

Stereoselective syntheses of the naturally occurring, cytotoxic lactone spicigerolide and three nonnatural stereoisomers thereof are described. The commercially available sugar l-rhamnose was in all cases the chiral starting material. Key steps in each of these syntheses were asymmetric Brown allylations and ring-closing metatheses. The cytotoxic activities of the four lactones against a range of tumoral lines were then determined.

StereochemistryRhamnoseStereoisomerismAntineoplastic AgentsMetathesisChemical synthesisRhamnosechemistry.chemical_compoundLactonesStructure-Activity RelationshipCell Line TumorCytotoxic T cellStructure–activity relationshipOrganic chemistryHumanschemistry.chemical_classificationCell DeathChemistryorganic chemicalsOrganic ChemistryStereoisomerismGeneral MedicineSpicigerolideAldoseCyclizationOrgan SpecificityStereoselectivityLactoneThe Journal of organic chemistry
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Water-soluble isoindolo[2,1-a]quinoxalin-6-imines: In vitro antiproliferative activity and molecular mechanism(s) of action

2015

Abstract Water-soluble isoindoloquinoxalin (IIQ) imines and the corresponding acetates were conveniently prepared from the key intermediates 2-(2′-aminophenyl)-2H-isoindole-1-carbonitriles obtained by a Strecker reaction between substituted 1,2-dicarbaldehydes and 1,2-phenylenediamines. Both series were screened by the National Cancer Institute (Bethesda, MD) and showed potent antiproliferative activity against a panel of 60 human tumor cell lines. Several of the novel compounds showed GI50 values at a nanomolar level on the majority of the tested cell lines. Among IIQ derivatives, methoxy substituents at positions 3 and 8 or/and 9 were especially effective in impairing cell cycle progressi…

StereochemistryStrecker amino acid synthesisAntineoplastic AgentsApoptosisIsoindolo[21-a]quinoxalin-6-imineTopoisomerase I inhibitorsTopoisomerase-I InhibitorMicrotubulesTubulinCell Line TumorQuinoxalinesDrug DiscoveryHumansCytotoxic T cellCell ProliferationPharmacologyTopoisomerase I inhibitorChemistryAntitubulin agents; G-quadruplex interaction; Isoindolo[2; 1-a]quinoxalin-6-imines; Topoisomerase I inhibitors; Drug Discovery3003 Pharmaceutical Science; Organic Chemistry; PharmacologyAntitubulin agentsDrug Discovery3003 Pharmaceutical ScienceCell CycleOrganic ChemistryWaterGeneral MedicineSettore CHIM/08 - Chimica FarmaceuticaIn vitroTelomereAntitubulin agentAntitubulin agents; G-quadruplex interaction; Isoindolo[21-a]quinoxalin-6-imines; Topoisomerase I inhibitors; Drug Discovery3003 Pharmaceutical Science; Organic Chemistry; Pharmacology1-a]quinoxalin-6-iminesDNA Topoisomerases Type ISolubilityBiochemistryCell cultureApoptosisIsoindolo[2Cancer cellIminesG-quadruplex interactionDrug Screening Assays Antitumor
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Cytotoxic activity of some natural and syntetic sesquiterpene lactones

2006

Several natural and synthetic sesquiterpene lactones with different skeletons were tested and found to be active against nine cancer cell lines. Elemane (4), heliangolane (5) and their hydroxy analogues 9 and 10, all containing an α,β-unsaturated aldehyde substituent, were the most potent compounds.

StereochemistrySubstituentPharmaceutical ScienceCentaureaPharmacognosySesquiterpeneAldehydeANTITUMOR AGENTSAnalytical Chemistrychemistry.chemical_compoundInhibitory Concentration 50LactonesStructure-Activity RelationshipCell Line TumorDrug DiscoveryStructure–activity relationshipOrganic chemistryCytotoxic T cellHumansCENTAUREA-PAUICytotoxicityPharmacologychemistry.chemical_classificationBiological ProductsMolecular StructureDERIVATIVESOrganic ChemistryCNICINSettore CHIM/06 - Chimica OrganicaAntineoplastic Agents PhytogenicComplementary and alternative medicinechemistryMolecular MedicineSesquiterpenesLactone
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Cytotoxicity and NMR Studies of Platinum Complexes with Cyclooctadiene Ligands

2014

The synthesis of a series of platinum complexes containing cyclooctadiene ligands with the general structure PtMeL(R-cod) (where L = Cl, I, nC3F7, iC3F7, nC8F17, Me, aryl, alkynyl and R = H, Me, Et, iPr, nBu, iBu, nHex, Ph) is presented. All complexes are remarkably stable and were obtained in excellent yields. Their structure in both solution and the solid state were explored by crystal structures and multinuclear (1H, 13C, 19F, 195Pt) NMR spectroscopy. Cytotoxicity experiments with selected complexes in HeLa cells revealed higher toxicity in comparison to that of cisplatin for most of the structures.

Stereochemistrychemistry.chemical_elementCrystal structure010402 general chemistry01 natural sciencesMedicinal chemistryInorganic ChemistryHeLachemistry.chemical_compoundmedicinePhysical and Theoretical ChemistryCytotoxicityta116Cisplatinbiology010405 organic chemistryArylOrganic ChemistryNuclear magnetic resonance spectroscopybiology.organism_classification3. Good health0104 chemical scienceschemistryPlatinumCyclooctadienemedicine.drugOrganometallics
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Synthesis, structural characterisation and biological studies of new mononuclear platinum(II) complexes with sterically hindered heterocyclic ligands

2011

Abstract Three novel cisplatin analogues were synthesized, designed according to an approach which violates the “classical” structure–activity relationship, by replacing the diamine ligands with a planar N donor heterocycle giving a sterically hindered complex. Moreover, the sterical hindrance of antitumor drug candidates potentially makes them less susceptible to deactivation by sulphur-containing proteins and helping to overcome resistance mechanisms. The resulting mononuclear complexes of sterically hindered polidentate heterocyclic N ligands [PtCl(bbp)]Cl ( 1 ) [bbp = 2,6-bis(2-benzimidazolyl)pyridine], [PtCl 2 (dptdn)](H 2 O) ( 2 ) [dptdn = sodium 5,6-diphenyl-3-(2′-pyridyl)-1,2,4-tria…

Steric effectsCisplatinStereochemistryCytotoxicitychemistry.chemical_elementBiological activityPolydentate nitrogen ligandInorganic Chemistrychemistry.chemical_compoundchemistryPolynuclear platinum complexeSettore CHIM/03 - Chimica Generale E InorganicaDiaminePyridineMaterials ChemistrymedicinePhysical and Theoretical ChemistryBifunctionalCytotoxicityPlatinummedicine.drugPolydentate nitrogen ligands; Polynuclear platinum complexes; Cytotoxicity
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Evidence against a key role for transforming growth factor-beta1 in cytomegalovirus-induced bone marrow aplasia.

1998

During immunodeficiency after sublethal haematoablative treatment, cytomegalovirus (CMV) infection interferes with haematopoietic reconstitution and can cause lethal bone marrow (BM) aplasia. The in vivo model of murine CMV infection has identified the BM stroma as the principal target site of CMV in the haematopoietic cord. The infected cell type is the reticular stromal cell which forms the stromal network and produces essential haemopoietins, such as stem-cell factor (SCF). The expression of SCF was found to be reduced in the infected stroma, but the stromal network was not disrupted and the number of infected stromal cells was too low to explain the functional deficiency. These facts ca…

Stromal cellmedicine.medical_treatmentCytomegalovirusGene ExpressionBone Marrow CellsBone Marrow AplasiaCD8-Positive T-LymphocytesKidneyVirus ReplicationMiceTransforming Growth Factor betaVirologymedicineAnimalsCytotoxic T cellBone Marrow DiseasesBone Marrow TransplantationMice Inbred BALB CbiologyTransforming growth factor betaVirologyHematopoiesisHaematopoiesisCytokinemedicine.anatomical_structureLiverCytomegalovirus Infectionsbiology.proteinFemaleImmunotherapyBone marrowStromal CellsTransforming growth factorJournal of General Virology
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