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

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• 作者：Paola Barraja^a ; Patrizia Diana^a ; Alessandra Montalbano^a ; Anna Carbone^a ; Giampietro Viola^b ; Giuseppe Basso^b ; Alessia Salvador^c ; Daniela Vedaldi^c ; Francesco Dall’ ; Acqua^c ; Girolamo Cirrincione^a ; ^{gcirrinc@unipa.it}
• 关键词：Pyrrolo[3 ; 4-h]quinolinones ; Angelicin heteroanalogues ; Photochemotherapy ; Phototoxicity
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2011
• 出版时间：1 April 2011
• 年：2011
• 卷：19
• 期：7
• 页码：2326-2341
• 全文大小：1339 K

文摘

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.