Thiopyrano[2,3-e]indol-2-ones: Angelicin heteroanalogues with potent photoantiproliferative activity

被引：18

作者：

Barraja, Paola ^{[1
]}

Diana, Patrizia ^{[1
]}

Montalbano, Alessandra ^{[1
]}

Carbone, Anna ^{[1
]}

Cirrincione, Girolamo ^{[1
]}

Viola, Giampietro ^{[2
]}

Salvador, Alessia ^{[2
]}

Vedaldi, Daniela ^{[2
]}

Dall'Acqua, Francesco ^{[2
]}

机构：

[1] Univ Palermo, Dipartimento Farmacochim Tossicol & Biol, I-90123 Palermo, Italy

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

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2008年 / 16卷 / 22期

关键词：

Thiopyrano[2,3-e]indol-2-ones; Angelicin; Antiproliferative activity; Photochemotherapeutic agents; Apoptosis;

D O I：

10.1016/j.bmc.2008.10.002

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：

A new class of compounds, the thiopyrano[2,3-e]indol-2-ones, bioisosters of the angular furocoumarin angelicin, was synthesized with the aim of obtaining new photochemotherapeutic agents. In particular 7,8-dimethyl-thiopyranoindolone 6c s showed a remarkable phototoxicity and a great dose UVA dependence reaching IC50 values at submicromolar level. This latter photoinduced a massive apoptosis and a remarkable photodamage to lipids and proteins. Although it did not intercalate DNA, it was able to cause photooxidation of DNA bases. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：9668 / 9683

页数：16

共 42 条

[1] Apoptosis induced by exposure to a low steady-state concentration of H2O2 is a consequence of lysosomal rupture [J].