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

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 IC50 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.

A new series of pyrroloquinolinones were synthesised and evaluated for their phototoxic activity. Some of the title compounds showed, upon UVA irradiation, IC50 values comparable or lower than angelicin used as reference drug.Figure optionsDownload as PowerPoint slide