Screening of probable carcinogenic agonists of Aryl Hydrocarbon Receptor (AhR) from various pesticides using computational molecular biology approach

Aryl hydrocarbon receptor (AhR) is a ligand-activated cytosolic transcription factor. Once activated AhR stimulates the pathways that are directly or indirectly linked to inflammation and breast cancer. Exogenous agonists of AhR including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and benzopyrene are found to be carcinogenic in nature. Breast cancer being the most prevalent cancer, makes it an important aspect to look for new exogenous agonists of AhR with carcinogenic properties. In this study, an effort has been made to screen new agonist from pesticides, which may have role in breast cancer development. Primarily, the structure of AhR PAS domain was determined by using SWISS-MODEL server. Thereafter, probable carcinogenic molecules from pesticides were screened and molecular docking studies were performed to identify potential binders with good energetics. Detailed structural analysis have resulted in four molecules namely, Isopyrazam, Noviflumuron, Oxyfluorfen and Resmethrin, that showed higher negative binding energy, when compared to TCDD. Molecular Dynamics Simulation studies of AhR- Isopyrazam were further carried out to prove the stability of the complex which suggests that presence of these agonist in different pesticides may have major role to play to cause breast cancer. Avoiding or minimizing the use of these compounds in the pesticides may be a strategy to combat breast cancer in future.