title: Synthesis of pyrrolo[3,2-h]quinolinones with good photochemotherapeutic activity and no DNA damage.
abstract: 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.
authors.affiliation: Dipartimento Farmacochimico, Tossicologico e Biologico, Università degli Studi di Palermo, Via Archirafi 32, 90123 Palermo, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Barraja
authors.forename: Libero
authors.initials: L
authors.lastname: Caracausi
authors.forename: Patrizia
authors.initials: P
authors.lastname: Diana
authors.forename: Anna
authors.initials: A
authors.lastname: Carbone
authors.forename: Alessandra
authors.initials: A
authors.lastname: Montalbano
authors.forename: Girolamo
authors.initials: G
authors.lastname: Cirrincione
authors.forename: Paola
authors.initials: P
authors.lastname: Brun
authors.forename: Giorgio
authors.initials: G
authors.lastname: Palù
authors.forename: Ignazio
authors.initials: I
authors.lastname: Castagliuolo
authors.forename: Francesco
authors.initials: F
authors.lastname: Dall'acqua
authors.forename: Daniela
authors.initials: D
authors.lastname: Vedaldi
authors.forename: Alessia
authors.initials: A
authors.lastname: Salvador
mesh_terms: D045744:Cell Line, Tumor; D004249:DNA Damage; D011564:Furocoumarins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D010718:Phosphatidylserines / Q000378:metabolism; D017319:Photosensitizing Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D011564:Furocoumarins; D010718:Phosphatidylserines; D017319:Photosensitizing Agents; D011758:Pyrroles; D011804:Quinolines; D017382:Reactive Oxygen Species; C410406:pyrroloquinoline; C011659:angelicin