6533b86dfe1ef96bd12c97db

RESEARCH PRODUCT

Pyrrolo[3,4-h]quinolinones a new class of photochemotherapeutic agents

Girolamo CirrincioneAlessia SalvadorFrancesco Dall'acquaPaola BarrajaDaniela VedaldiAlessandra MontalbanoGiampietro ViolaPatrizia DianaGiuseppe BassoAnna Carbone

subject

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 Fractions

description

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, alteration of cell cycle profile and membrane lipid peroxidation.

yearjournalcountryeditionlanguage
2011-01-01Bioorganic & Medicinal Chemistry
https://doi.org/10.1016/j.bmc.2011.02.023