Potential of paracetamol for reproductive disruption: molecular interaction, dynamics, and MM-PBSA based in-silico assessment

Abstract

Paracetamol is generally recommended for pain and fever. However, as per experimental and epidemiological data, widespread and irrational or long-term use of paracetamol may be harmful to human endocrine homeostasis, especially during pregnancy. Some researchers suggest that prenatal exposure to paracetamol might alter fetal development and also enhance the risk of reproductive disorders. An imbalance in the levels of these hormones may play a significant role in the emergence of various diseases, including infertility. Therefore, in this study, the interaction mechanism of paracetamol with reproductive hormone receptors was investigated by molecular docking, molecular dynamics (MD) simulations, and Poisson–Boltzmann surface area (MM-PBSA) for assessing paracetamol’s potency to disrupt reproductive hormones. The results indicate that paracetamol has the ability to interact with reproductive hormone receptors (estrogen 1XP9; 1QKM with binding energy of −5.61 kcal/mol; −5.77 kcal/mol; androgen 5CJ6 − 5.63 kcal/mol; and progesterone 4OAR -5.60 kcal/mol) by hydrogen bonds as well as hydrophobic and van der Waals interactions to maintain its stability. In addition, the results of the MD simulations and MM-PBSA confirm that paracetamol and reproductive receptor complexes are stable. This research provides a molecular and atomic level understanding of how paracetamols disrupt reproductive hormone synthesis. The root mean square deviation (RMSD), root mean square fluctuation (RMSF), Radius of Gyration and hydrogen bonding exhibited that paracetamol mimic at various attribute to bisphenol and native ligand.