Construction of simplified models to simulate estrogenic disruptions by esters of 4-hydroxy benzoic acid (parabens)

Four parabens (methyl. n-butyl, benzyl and isobutylparaben) were theoretically studied in order to evaluate their estrogenic activity through simplified models. The experimental structure of the human estrogen receptor ligand-binding domain in complex with 17 beta-estradiol was used as the starting point to construct the models. The complex between 17 beta-estradiol and three fragments of the estrogenic receptor (Arg, Glu and His), resulted in a reasonable simplified model of interaction. The replacement of 17-beta-estradiol by parabens was evaluated by conformational analyses and interaction energy calculations at BHandHLYP/cc-PVTZ(-f)+ level of theory. According with the calculated interaction energies, methylparaben is the paraben with higher estrogenic activity, which is in agreement with experimental studies of extraction and quantification of parabens in tumors. The antibacterial activity of parabens was also explored considering the formation of potassium salts in the phenolic CH groups. From the obtained relative energy values, methylparaben is the most active preservative. (c) 2008 Elsevier B.V. All rights reserved.