Effects of Diazinon in endocrine disruption: molecular docking and dynamics simulation on hormonal receptors in the context of the extensive use

Abstract

Diazinon (DZN) was extensively utilized as an organophosphorus pesticide in developing countries. DZN has the ability to generate distinct metabolites, namely diazinon-oxon (DZNO) and 2-isopropyl-6-methyl-4-hydroxypyrimidine (IMHP), as well as non-specific metabolites diethylthiophosphate (DETP) and diethylphosphate (DEP). The aim of this study was to use computational methods to identify possible ways in which DZN and its main metabolites interact with estrogen, progesterone and estrogen-related receptors. This was done by in silico molecular docking. Molecular docking and dynamics simulation were conducted to comprehend the molecular interaction between diazinon and its metabolites (DZNO and DETP) with the human receptors. Chronic sublethal exposure to this insecticide is known to cause harmful effects on the metabolism of sex hormones and the functioning of the nervous system. This substance is believed to be an endocrine-disrupting agent and is known to produce aberrant patterns of development, shrinkage of the gonads, and issues with neurodevelopment. The metabolites produced during the metabolism of diazinon can bind to estrogen and progesterone receptors, specifically human progesterone receptor (hPR), estrogen-related receptor alpha (ERRα), estrogen-related receptor gamma (ERRγ) estrogen receptor alpha (Erα) and estrogen receptor beta (Erβ). This binding has the potential to interfere with estrogen and progesterone signaling in humans. These compounds provide a possible danger of interfering with estrogen and progesterone signaling in humans.