Synthesis of pyrrolo[3,2-h]quinolinones with good photochemotherapeutic activity and no DNA damage.
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.
Barraja
Paola
P
Dipartimento Farmacochimico, Tossicologico e Biologico, Università degli Studi di Palermo, Via Archirafi 32, 90123 Palermo, Italy.
Caracausi
Libero
L
Diana
Patrizia
P
Carbone
Anna
A
Montalbano
Alessandra
A
Cirrincione
Girolamo
G
Brun
Paola
P
Palù
Giorgio
G
Castagliuolo
Ignazio
I
Dall'acqua
Francesco
F
Vedaldi
Daniela
D
Salvador
Alessia
A
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
D011564:Furocoumarins; D010718:Phosphatidylserines; D017319:Photosensitizing Agents; D011758:Pyrroles; D011804:Quinolines; D017382:Reactive Oxygen Species; C410406:pyrroloquinoline; C011659:angelicin