6533b86efe1ef96bd12cc9b8

RESEARCH PRODUCT

SYNTHESIS OF PYRROLO[3,2-H]QUINOLINONES WITH GOOD PHOTOCHEMOTHERAPEUTIC ACTIVITY AND NO DNA DAMAGE

Girolamo CirrincioneIgnazio CastagliuoloAlessia SalvadorLibero CaracausiGiorgio PalùPatrizia DianaPaola BarrajaDaniela VedaldiPaola BrunFrancesco Dall'acquaAnna CarboneAlessandra Montalbano

subject

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

description

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.

yearjournalcountryeditionlanguage
2010-01-01
10.1517/17425240903362410http://hdl.handle.net/10447/51294