The androgen receptor is a ligand-dependent nuclear transcription factor that regulates the expression of numerous genes involved in the development and function of various tissues. Dysfunction of the androgen receptor is associated with the development of numerous diseases, including prostate cancer, which is closely linked to androgen signaling and represents one of the most common malignant diseases in men. For this reason, the androgen receptor represents an important therapeutic target, and increasing attention is being directed toward the investigation of compounds that can modulate its function, such as agonists, antagonists, and selective androgen receptor modulators. Agonists are therapeutically useful in conditions with reduced receptor activity, while antagonists are crucial in diseases where androgen signaling promotes pathological cell proliferation, particularly in prostate cancer and benign prostatic hyperplasia. The aim of this master’s thesis was to evaluate the effects of selected 4-substituted 1,3-dinitrobenzenes on the androgen receptor and to assess their potential agonistic or antagonistic effects. First, we evaluated their effects using the predictive in silico model Endocrine Disruptome. We selected the AR-EcoScreen cell line as the in vitro model. The cells were first exposed to concentrations of 10 µM, 1 µM, 100 nM, 10 nM, 1 nM, and 100 pM, and cell viability was assessed using the resazurin assay. To functionally assess the activity of the compounds, we then performed a luciferase reporter assay to determine the transcriptional activity of the androgen receptor in accordance with OECD guidelines. None of the tested compounds exhibited agonistic activity, while all demonstrated antagonistic effects. Compound LJB02 exhibited statistically significant antagonistic activity at concentrations higher than 1 nM, compounds LJB05 and LJB07 at concentrations higher than 100 pM, and compound LJB06 at concentrations higher than 100 nM. Compounds LJB05 and LJB07 exhibited the most pronounced antagonistic effect, even at the lowest tested concentrations (100 pM). Furthermore, we observed differences in antagonistic activity between the tetrazole (LJB06) and triazole (LJB07) derivatives, with the triazole derivative exhibiting stronger antagonistic activity, as reflected in a greater reduction in transcriptional activity. With the obtained results, we confirmed that the selected compounds have the potential to modulate the androgen receptor and that their chemical structure significantly influences their activity.
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