Estrogenic Activity of Branched 4-Nonylphenol Isomers Examined by Yeast Two-Hybrid Assay

Abstract

Various branched isomers of 4-nonylphenol (NP) and, in addition, the other 4-alkylphenols (APs) were synthesized and their estrogenic activities were assessed using the yeast two-hybrid system. We investigated the relationships between the structure of the nonyl group of NP isomers and their estrogenic activities based on the following five factors: the length of the main alkyl chain, the degree of branching on the α-carbon, the degree of bulkiness, the position of the branch, and the cyclic structure in the nonyl group. An appropriate length of the main alkyl chain was essential for the estrogenic activity. A small effect of the branching on the α-carbon was observed. The importance of the bulkiness and position of the branch in the nonyl group was suggested from the results of the synthesized NP isomers possessing the high estrogenic activities. The bulkiness on the β-carbon was the most important factor for the high estrogenic activity. The investigation of the cyclic structure also indicated the significance of the bulkiness around the β-carbon. The bulkiness on the γ-carbon was also suggested to be an important factor. The metabolic effect of the synthesized APs on the estrogenic activity was also examined using a liver S9. The estrogenic activities of the selected APs were either reduced or lost. In addition, GC-MS analyses of the commercial NP and synthesized NP isomers revealed that the nine synthesized NP isomers were included in the commercial NP.

Environmental fate of phenolic endocrine disruptors: field and laboratory studies

“…Despite the difference in cell reporter systems used and except for one NP isomer, the oestrogenicity rankings of the three studies were in excellent agreement. The results of the three studies also well support the hypothesis of Shioji et al (2006) that an optimal length of the main alkyl chain (four to six carbon atoms) together with bulkiness around the β-and γ -position is necessary for high oestrogenicity, whereas the presence of α-substituents is less important.…”

“…Three recent studies clearly demonstrate that NP isomers differ in oestrogenic activity (Preuss et al 2006;Shioji et al 2006;Gabriel et al 2008). Figure 6 shows the response of the yeast oestrogen screen (YES) to various concentrations of a range of NP isomers .…”

Estrogenic effects along the river saale

“…The ethoxylates are degraded to alkylphenols, which in turn are released by industrial and municipal sewage treatment plants [10][11][12]. Iso-nonylphenols act as xenoestrogens by the activation of the estrogen receptor [13][14][15].…”

Optical Resolution and Absolute Configuration of Branched 4-Nonylphenol Isomers and Their Estrogenic Activities

“…10,11) Consequently, in the field of NP research, it is absolutely necessary to consider NPs from an isomer-specific viewpoint. 12) Although a few groups have reported the synthesis of NP isomers, [13][14][15][16][17] all of these NP isomers were optically inactive (racemic) compounds. In our previous studies, we described preparative fractionation of a commercial NP mixture using HPLC to afford fourteen NP isomers (Fig.…”