Molecular interactions of bisphenols and analogs with glucocorticoid biosynthetic pathway enzymes: an in silico approach

Glucocorticoids are known to have vital effects on metabolism, behavior and immunity. Any sort of impairment in their synthesis may lead to the generation of numerous ill health effects. Different environmental toxicants, including bisphenols and their analogs pose deleterious effect on the biosynthesis of glucocorticoids, thereby leading to endocrine disruption. In order to assess the effect of these environmental toxicants on gluocorticoid biosynthetic pathway, an in silico study was performed. This involved molecular docking studies of 18 ligands with the selected participating enzymes of the pathway. These enzymes were CYP11A1, CYP11B2, CYP19A1, CYP17A1, 3 alpha/20 beta-HSD, 3 alpha/17 beta-HSD and CYP21A2. Comparison of their binding affinity was made with the known inhibitors of these enzymes. In case of CYP11A1, Bisphenol M (BP M) had the lowest docking score (D score) of -8.699 kCal/mol, and was better than that of the standard, Metyrapone. Bisphenol PH (BP PH) was found to have significant affinity with CYP11B2. In case CYP19A1, results were found to be comparable with the standards, Exemestane and Letrozole. BP PH elicited better results than the standard Abiraterone acetate against CYP17A1. BP M had a D score of -7.759 against 3 alpha/20 beta-HSD, again better results than the standard, Trilostane. Upon molecular docking of BP PH against CYP21A2, it was seen that amongst all the analogs, it had maximum interactions along with the lowest D score. From all the above instances mentioned, it is quite evident that certain BPA analogs have more potential to modulate the enzymes involved in comparison to the known inhibitors.