Search results for "Angelicin heteroanalogue"

showing 4 items of 4 documents

Pyrano[2,3-e]isoindol-2-ones, new angelicin heteroanalogues

2009

A convenient synthesis of the pyrano[2,3-e]isoindol-2-one ring system, an heteroanalogue of angelicin, is reported. Our synthetic approach consists of the annelation of the pyran ring on the isoindole moiety using 5-dialkylamino- or 5-hydroxymethylene intermediates as building blocks. The photoantiproliferative activity of the new derivatives was studied. Some of them bearing the benzyl group at the 8 position were active with IC(50) in the micromolar range. Cell cytotoxicity involves apoptosis, alteration of cell cycle profile and membrane photodamage.

AnnulationPyrano-isoindolesStereochemistryChemistry PharmaceuticalClinical BiochemistryPharmaceutical ScienceApoptosisIsoindolesRing (chemistry)BiochemistryChemical synthesisInhibitory Concentration 50Jurkat CellsStructure-Activity Relationshipchemistry.chemical_compoundAngelicinCell Line TumorFurocoumarinsDrug DiscoveryHumansMoietyMolecular BiologyPyransMolecular StructurePyrano-isoindoleChemistryPhotochemotherapeutic activityOrganic ChemistryPyrano-isoindoles; Angelicin heteroanalogues; Photochemotherapeutic activity; ApoptosisSettore CHIM/08 - Chimica FarmaceuticaAngelicin heteroanaloguesOxygenModels ChemicalPyranDrug DesignBenzyl groupMolecular MedicineK562 CellsIsoindoleAngelicin heteroanalogueBioorganic & Medicinal Chemistry Letters
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Synthesis of the New Ring System 2-Oxo-[1,4]oxazino[3,2-e]indole, Heteroanalogue of Angelicin

2009

A convenient synthesis of the 2-oxo-[1,4]oxazino[3,2-e]indole ring system, an heteroanalogue of Angelicin, is reported. Our synthetic approach consisted of the annelation of the oxazine ring on the indole moiety using 4-amino-5-hydroxy indoles as building blocks. The antiproliferative activity of the new compounds either in the dark or under UVA irradiation was investigated.

Indole testAnnulationStereochemistryOrganic Chemistry1; 4-Oxazinoindoles; 1; 4-Benzoxazines; Angelicin heteroanalogue; 4-Amino-5-hydroxy indoles114-Benzoxazine14-OxazinoindoleRing (chemistry)Biochemistry4-Oxazinoindoles4-Benzoxazineschemistry.chemical_compoundAngelicinchemistryDrug DiscoveryMoiety4-Amino-5-hydroxy indolesUva irradiationAngelicin heteroanalogue
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SYNTHESIS OF PYRROLO[3,2-H]QUINOLINONES WITH GOOD PHOTOCHEMOTHERAPEUTIC ACTIVITY AND NO DNA DAMAGE

2010

In the search for new photochemotherapeutic agents, a series of derivatives of the ring system pyrrolo[3,2-h]quinoline--bioisosters of the angular furocoumarin angelicin--were synthesized through a four-step synthetic approach, in reasonable overall yields. Eight of the synthesized derivatives showed a remarkable phototoxicity against a panel of four human tumor cell lines and a great dose UV-A dependence, reaching IC₅₀ values at submicromolar level. The mode of cellular death photoinduced by pyrrolo[3,2-h]quinolines was evaluated through a series of flow cytometric analysis and other tests were performed to clarify their mechanism of action.

PYRROLO[32-H]QUINOLINONESStereochemistryDNA damageClinical BiochemistryPharmaceutical SciencePhosphatidylserinesBiochemistryChemical synthesischemistry.chemical_compoundCell Line TumorFurocoumarinsDrug Discovery2-H]QUINOLINONESmedicineHumansPyrrolesPhotosensitizerMolecular BiologyMembrane Potential MitochondrialPhotosensitizing AgentsPYRROLO[3; 2-H]QUINOLINONES; ANGELICIN HETEROANALOGUES; PHOTOCHEMOTHERAPY; PHOTOTOXICITYFurocoumarinOrganic ChemistryBiological activitySettore CHIM/08 - Chimica FarmaceuticaPHOTOCHEMOTHERAPYPHOTOTOXICITYPYRROLO[3ANGELICIN HETEROANALOGUESMechanism of actionchemistryQuinolinesLactamMolecular Medicinemedicine.symptomReactive Oxygen SpeciesPhototoxicityDNA Damage
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Pyrrolo[3,4-h]quinolinones a new class of photochemotherapeutic agents

2011

Abstract Pyrrolo[3,4- h ]quinolin-2-ones were synthesized as nitrogen isosters of the angular furocoumarin angelicin, with the aim of obtaining new photochemotherapeutic agents with increased antiproliferative activity and lower undesired toxic effects. A versatile synthetic pathway was approached to allow the isolation of derivatives of the new ring system with a good substitution pattern on the pyrrole moiety. Photobiological screenings of the new compounds revealed a potent phototoxic effect and a great UVA dose dependence, reaching IC 50 values at submicromolar level. The induced cellular photocytotoxicity was related to apoptosis with the involvement of mitochondria and lysosomes, alte…

Pyrrolo[3; 4-h]quinolinones; Angelicin heteroanalogues; Photochemotherapeutic agents; PhototoxicityStereochemistryClinical BiochemistryMembrane lipid peroxidationPharmaceutical ScienceHL-60 CellsPhosphatidylserinesQuinolonesMitochondrionBiochemistryPhototoxicityJurkat CellsStructure-Activity Relationshipchemistry.chemical_compoundPhotochemotherapeutic agentsAngelicinCell Line TumorDrug DiscoveryHumansMoietyFluorometryPyrrolesPyrrolo[3Molecular BiologyPyrrolePyrrolo[34-h]quinolinoneFurocoumarinCell CycleOrganic Chemistry4-h]quinolinonesDNAPhotochemical ProcessesSettore CHIM/08 - Chimica FarmaceuticaAngelicin heteroanaloguesPhotochemotherapeutic agentPhotochemotherapychemistryApoptosisMolecular MedicineLipid PeroxidationPhototoxicityAngelicin heteroanalogueSubcellular FractionsBioorganic & Medicinal Chemistry
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