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

被引：38

作者：

Barraja, Paola ^{[1
]}

Diana, Patrizia ^{[1
]}

Montalbano, Alessandra ^{[1
]}

Carbone, Anna ^{[1
]}

Viola, Giampietro ^{[2
]}

Basso, Giuseppe ^{[2
]}

Salvador, Alessia ^{[3
]}

Vedaldi, Daniela ^{[3
]}

Dall'Acqua, Francesco ^{[3
]}

Cirrincione, Girolamo ^{[1
]}

机构：

[1] Univ Palermo, Dipartimento Sci & Tecnol Mol & Biomol, Sez Chim Farmaceut & Biol, I-90123 Palermo, Italy

[2] Univ Padua, Dipartimento Pediat, Lab Oncoematol, I-35128 Padua, Italy

[3] Univ Padua, Dipartimento Sci Farmaceut, I-35131 Padua, Italy

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2011年 / 19卷 / 07期

关键词：

Pyrrolo[3,4-h]quinolinones; Angelicin heteroanalogues; Photochemotherapy; Phototoxicity; HUMAN SKIN FIBROBLASTS; ANGULAR FUROQUINOLINONES; BIOLOGICAL-ACTIVITY; STRAND BREAKS; DNA; PHOTOSENSITIZATION; APOPTOSIS; PSORALEN; DAMAGE; MITOCHONDRIA;

D O I：

10.1016/j.bmc.2011.02.023

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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. (C) 2011 Elsevier Ltd. All rights reserved.

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页码：2326 / 2341

页数：16

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