1. Academic Validation
  2. Pyrrolo[3,4-h]quinolinones a new class of photochemotherapeutic agents

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

  • Bioorg Med Chem. 2011 Apr 1;19(7):2326-41. doi: 10.1016/j.bmc.2011.02.023.
Paola Barraja 1 Patrizia Diana Alessandra Montalbano Anna Carbone Giampietro Viola Giuseppe Basso Alessia Salvador Daniela Vedaldi Francesco Dall'Acqua Girolamo Cirrincione
Affiliations

Affiliation

  • 1 Dipartimento di Scienze e Tecnologie Molecolari e Biomolecolari, Sezione di Chimica Farmaceutica e Biologica, Università degli Studi di Palermo, Via Archirafi 32, Palermo 90123, Italy.
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.

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