Affinities of organophosphate flame retardants to tumor suppressor gene p53: an integrated in vitro and in silico study.

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Li F, Cao L, Li X, Li N, Wang Z, Wu H

Affinities of organophosphate flame retardants to tumor suppressor gene p53: an integrated in vitro and in silico study.

Toxicol Lett. 2015 Jan 22;232(2):533-41. doi: 10.1016/j.toxlet.2014.12.006. Epub 2014 Dec 12.

PubMed ID

25510514 [ View in PubMed

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Abstract

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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Triethyl phosphate	Cellular tumor antigen p53	Protein	Humans	Unknown	Not Available	Details