pyrroloquinoline and angelicin

Heteroanalogues of angelicin, pyrrolo[3,2-h]quinazolines, were synthesized with the aim of obtaining new potent photochemotherapeutic agents. Many derivatives caused a significant decrease in cell proliferation in several human tumor cell lines after irradiation with UVA light (GI(50) =15.2-0.2 μM). Their phototoxicity effected apoptosis in Jurkat cells with the involvement of mitochondria (as determined by the loss of mitochondrial membrane potential and production of reactive oxygen species) and lysosomes. The phototoxicity of these compounds could be explained by lipid peroxidation.

Topics: Apoptosis; Cell Line, Tumor; Drug Screening Assays, Antitumor; Furocoumarins; Humans; Photosensitizing Agents; Pyrroles; Quinolines; Reactive Oxygen Species; Structure-Activity Relationship; Ultraviolet Rays

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.

Topics: Cell Line, Tumor; DNA Damage; Furocoumarins; Humans; Membrane Potential, Mitochondrial; Phosphatidylserines; Photosensitizing Agents; Pyrroles; Quinolines; Reactive Oxygen Species