点击次数：

论文类型：期刊论文

发表时间：2015-01-22

发表刊物：TOXICOLOGY LETTERS

收录刊物：SCIE、PubMed、Scopus

卷号：232

期号：2

页面范围：533-541

ISSN号：0378-4274

关键字：Organophosphate flame retardants (OPFRs); p53; Docking; Quantitative structure-activity relationship (QSAR); Binding affinity; Partial least squares (PLS)

摘要：Health concerns have been raised in regards to the environmental impact of the more frequently used organophosphate flame retardants (OPFRs). In this study, the effects of two typical OPFRs (TCPP and TPhP) on p53 gene expression in human embryo liver L02 cells were determined by quantitative real-time PCR. To better understand the relationship between molecular structural features of OPFRs and binding affinities for the tumor suppressor genes p53, an integrated experimental and in silico approach was used. The interaction of 9 OPFRs with p53 DNA fragment under simulated physiological conditions (phosphate buffer solution of pH 7.40), was explored by UV absorption spectroscopy, fluorescence spectroscopy and molecular modeling method. The binding constants of 9 OPFRs with p53 DNA fragment were determined respectively, using ethidium bromide (EB) as fluorescence probe of DNA. From docking analysis, hydrogen bonding and hydrophobic interactions were found to be the dominant interactions. Based on the observed interactions, appropriate molecular structural parameters were adopted to develop a quantitative structure-activity relationship (QSAR) model. The binding affinities of OPFRs to p53 DNA fragment were related with molecular electrostatic potential. The developed QSAR model had good robustness, predictive ability and mechanism interpretability. (c) 2014 Elsevier Ireland Ltd. All rights reserved.