Study of structure-activity relationship of AhR ligand using toxicological information

<p>Aromatic hydrocarbon receptor (AHR) is one of the transcription factors expressed in most cells and tissues in humans, and its transcriptional activation is caused by binding to a ligand. Since AHR ligands are also present in chemicals and drugs in air pollution and in food, it can be said that AHR ligands are closely related to maintaining human health. In this study, ligands, we analyzed the structure-activity relationship of AHR ligands, which are known to be particularly harmful in the air, and natural substances based on molecular structure and toxicity information for a comprehensive understanding of AHR. For the harmful substances in the air, we selected 33 substances known to be present in diesel exhaust. As for natural substances, 14 substances derived from plants were selected. Toxicity information and molecular structure were collected from Biological Test Results and SD files of the public database PubChem. Subsequently, the relationship with the structure / toxicity information was analyzed using ADMET predictor 9.5. As a result, it was found that many of the polycyclic aromatic compounds had more physiological activities of multiple nuclear receptors than the oxidative stress response. On the other hand, the physiological activity data of natural substances was not available, and it was presumed from the structure that there was a response through the AhR transcription activity.</p>