Per- and polyfluoroalkyl substances are a large family of synthetic chemicals that represent an indispensable raw material for the production of various products. In addition to the beside positive characteristics, the use of these substances has also some negative aspects. These are "eternal" chemicals that are highly resistant to degradation. Excessive accumulation of these substances in the environment can lead to many adverse health effects, including disturbances in the functioning of the hormonal system. Based on this, they were classified as endocrine disrupting chemicals.
In the master's thesis, we evaluated the potential endocrine action of 26 selected per- and polyfluoroalkyl substances. With the help of the freely available computer program Endocrine Disruptome, we checked the probability of binding of these compounds to 14 different nuclear receptors. Based on the obtained results and data from the databases, the compounds were divided into four groups. We divided them based on whether they are identified as potential endocrine disruptors and whether the program placed them in the red or orange class. For each compound, we checked professional literature whether the influence on a certain receptor was proved and thus we evaluated the adequacy of the program's predictions. We found that the program most often predicted the interactions with androgen, estrogen, mineralocorticoid and thyroid receptors. It correctly predicted the interactions of 11 out of 21 compounds with androgen receptors. Estrogen receptor interaction predictions were matched with data from studies only for a few compounds. The program correctly predicted interactions with thyroid receptors for six compounds. For some compounds, the predictions were not correct, and in most cases we could not evaluate the suitability of the program due to the lack of data from the studies. For the same reason, we could not adequately evaluate interactions with mineralocorticoid receptors. The program did not correctly predict interactions with peroxisome proliferator-activated receptors. The compounds, which the Endocrine Disruptome program placed in the red or orange class with androgen, estrogen, mineralocorticoid or thyroid receptors, were also checked with the 1-Click Docking program. As a comparison compound, we used the confirmed endocrine disruptor bisphenol A. We found that the results of the two programs matched. For most of the selected compounds, we predicted a higher binding affinity with nuclear receptors than bisphenol A.
Due to the lack of data in the literature, we could not confirm that the Endocrine Disruptome program is a reliable tool for predicting interactions with nuclear receptors for the studied group of compounds. Appropriate in vitro and in vivo methods would be necessary to confirm the endocrine effects, and this program could be used as one of the screening methods for the evaluation of the endocrine action of the considered compounds.
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