Theoretical Studies on the Quantitative Structure–Toxicity Relationship of Polychlorinated Biphenyl Congeners Reveal High Affinity Binding to Multiple Human Nuclear Receptors

Abstract

Polychlorinated biphenyls (PCBs) are organic chemicals consisting of a biphenyl structure substituted with one to ten chlorine atoms, with 209 congeners depending on the number and position of the chlorine atoms. PCBs are widely known to be endocrine-disrupting chemicals (EDCs) and have been found to be involved in several diseases/disorders. This study takes various molecular descriptors of these PCBs (e.g., molecular weight) and toxicity endpoints as molecular activities, investigating the possibility of correlations via the quantitative structure–toxicity relationship (QSTR). This study then focuses on molecular docking and dynamics to investigate the docking behavior of the strongest-binding PCBs to nuclear receptors and compares these to the docking behavior of their natural ligands. Nuclear receptors are a family of transcription factors activated by steroid hormones, and they have been investigated to consider the impact of PCBs on humans in this context. It has been observed that the docking affinity of PCBs is comparable to that of the natural ligands, but they are inferior in terms of stability and interacting forces, as shown by the RMSD and total energy values. However, it is noted that most nuclear receptors respond to PCBs similarly to how they respond to their natural ligands—as shown in the RMSF plots—the most similar of which are seen in the ER, THR-β, and RAR-α. However, this study is performed purely in silico and will need experimental verification for validation.

Modular Hub Genes in DNA Microarray Suggest Potential Signaling Pathway Interconnectivity in Various Glioma Grades

“…Through the DRE webserver, potential drug candidates were screened, as shown in Table 3, along with their corresponding pathways and affected processes based on their mechanism of action. Norgestimate, ethisterone, and nomegestrol are synthetic progestin hormones that mimic the effects of progesterone to activate physiological responses through binding with progesterone receptors [55][56][57]. The influence of sex hormones on glioma progression was observed in women, who are otherwise less likely to develop glioma than men but who become more prone to developing glioma after menopause due to decreased estrogen production [58][59][60].…”