Design, Synthesis and In Vitro Activity of Anticancer Styrylquinolines. The p53 Independent Mechanism of Action

被引：38

作者：

Mrozek-Wilczkiewicz, Anna ^{[1
,2
]}

Spaczynska, Ewelina ^{[3
]}

Malarz, Katarzyna ^{[3
]}

Cieslik, Wioleta ^{[3
]}

Rams-Baron, Marzena ^{[1
,2
]}

Krystof, Vladimir ^{[4
,5
]}

Musiol, Robert ^{[3
]}

机构：

[1] Univ Silesia, A Chelkowski Inst Phys, Katowice, Poland

[2] Univ Silesia, Silesian Ctr Educ & Interdisciplinary Res, Chorzow, Poland

[3] Univ Silesia, Inst Chem, Katowice, Poland

[4] Palacky Univ, Lab Growth Regulators, Ctr Reg Hana Biotechnol & Agr Res, CR-77147 Olomouc, Czech Republic

[5] Inst Expt Bot AS CR, Olomouc, Czech Republic

来源：

PLOS ONE | 2015年 / 10卷 / 11期

关键词：

BIOLOGICAL-ACTIVITY SPECTRUM; INTEGRASE INHIBITORS; MITOCHONDRIAL-DNA; CP-31398; ANALOGS; APOPTOSIS; REACTIVATION; DERIVATIVES; SERIES; AGENTS;

D O I：

10.1371/journal.pone.0142678

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

A group of styrylquinolines were synthesized and tested for their anti-proliferative activity. Anti-proliferative activity was evaluated against the human colon carcinoma cell lines that had a normal expression of the p53 protein (HCT116 p53(+/+)) and mutants with a disabled TP53 gene (HCT116 p53(-/-)) and against the GM 07492 normal human fibroblast cell line. A SAR study revealed the importance of Cl and OH as substituents in the styryl moiety. Several of the compounds that were tested were found to have a marked anti-proliferative activity that was similar to or better than doxorubicin and were more active against the p53 null than the wild type cells. The cellular localization tests and caspase activity assays suggest a mechanism of action through the mitochondrial pathway of apoptosis in a p53-independent manner. The activity of the styrylquinoline compounds may be associated with their DNA intercalating ability.

引用

页数：14

共 44 条

[1] Anticancer DNA intercalators cause p53-dependent mitochondrial DNA nucleoid re-modelling [J].