Computational models reveal the potential of polycyclic aromatic hydrocarbons to inhibit aromatase, an important enzyme of the steroid biosynthesis pathway

Abstract

Polycyclic aromatic hydrocarbons (PAHs) are widespread toxic chemicals that may cause endocrine disruption via interaction with aromatase (CYP19A1) which is a vital enzyme of steroid biosynthesis pathway. Herein, we report the optimization of PAHs and oxy-PAHs employing density functional theory (DFT) with B3LYP/3-21G basis set to elucidate their frontier molecular orbitals, Mulliken charges as well as the chemical reactivity descriptors. The DFT outcome revealed that Indeno(1,2,3-cd)pyrene show the lowest HOMO-LUMO gap (3.42 Kcal/mol) as well as highest electrophilicity index and basicity. To assess the structure based inhibitory action of PAHs and their metabolites, these were docked into the active site cavity of CYP19A1. The docking simulation studies predicted that Indeno(1,2,3-cd)pyrene has the least binding energy (-10.76 Kcal/mol) which is in good agreement with the DFT calculations and might serve as a potent inhibitor to CYP19A1 comparable with its known inhibitor, exemestane which has binding affinity −11.73 Kcal/mol. The high binding affinity of oxy-PAHs was attributed to the presence of hydrogen bonds along with different hydrophobic interactions between the pollutant and the critical amino acids residues of the receptor. The results emphasized that PAHs can structurally mimic the binding pattern of exemestane to aromatase.