Predicting The Toxicity of Emerging Pollutants via Molecular Docking: Interaction of Polyhalogenated Carbazoles with Human Androgen Receptor

Polyhalogenated carbazoles (PHCZs) are persistent chemical pollutants increasingly detected in different environmental matrices. They are structurally and chemically similar to other persistent organic pollutants (POPs), which are capable of disrupting the endocrine systems. However, PHCZs such as 3-chloro-9H-carbazole (3-CCZ), 3-bromo-9H-carbazole (3-BCZ), and 36-dibromo-9H-carbazole (36-BCZ) are rarely discussed in the context of their adverse effects on human health. Using molecular docking to investigate the potential toxicity of these PHCZs with the human androgen receptor (AR), this study finds that 36-dibromo-9H-carbazole and 3-bromo-9H-carbazole are potential AR antagonists, with the former being more toxic than the latter. This finding is on account of the presence of both Asn705 and Thr877 in the hydrophobic interaction of 36-BCZ, while only Thr877 is found in the hydrophobic interaction of 3-BCZ. Hence, PHCZs with higher bromine substitutions are more likely to be endocrine disruptors. Moreover, their binding sites with the human androgen receptor are similar to that of the androgen (agonist). Therefore, this study suggests that PHCZs may readily penetrate and disrupt the human androgen receptor (AR), providing the groundwork for future research studies and experimental validation on the molecular docking employed.