Akinola Lukman K, Uzairu Adamu, Shallangwa Gideon A, Abechi Stephen E
Department of Chemistry, Ahmadu Bello University, Zaria, Nigeria.
Department of Chemistry, Bauchi State University, Gadau, Nigeria.
Curr Res Toxicol. 2021 Sep 30;2:357-365. doi: 10.1016/j.crtox.2021.09.003. eCollection 2021.
Polychlorinated dibenzofurans (PCDFs) are known to cause endocrine disruption in humans and wildlife but the mechanisms underlying this disruption have not been adequately investigated. In this paper, the susceptibility of the endocrine system to disruption by PCDF congeners via nuclear receptor binding was studied using molecular docking simulation. Findings revealed that some PCDF congeners exhibit high probabilities of binding to androgen receptor in its agonistic and antagonistic conformations. In depth molecular docking analysis of the receptor-ligand complexes formed by PCDFs with androgen receptor in its agonistic and antagonistic conformations showed that, these complexes were stabilized by electrostatic, van der Waals, pi-effect and hydrophobic interactions. It was also observed that PCDF molecules mimic the modes of interaction observed in androgen-testosterone and androgen-bicalutamide complexes, utilizing between 65 and 83% of the amino acid residues used by the co-crystallized ligands for binding. This computational study suggests that some PCDF congeners may act as agonists and antagonists of androgen receptor in humans and wildlife via inapproprate binding to the receptor.
多氯二苯并呋喃（PCDFs）已知会导致人类和野生动物的内分泌紊乱，但这种紊乱背后的机制尚未得到充分研究。在本文中，利用分子对接模拟研究了内分泌系统对PCDF同系物通过核受体结合而受到干扰的敏感性。研究结果表明，一些PCDF同系物在其激动和拮抗构象中表现出与雄激素受体结合的高概率。对PCDFs与处于激动和拮抗构象的雄激素受体形成的受体-配体复合物进行深入的分子对接分析表明，这些复合物通过静电、范德华力、π效应和疏水相互作用得以稳定。还观察到，PCDF分子模仿了在雄激素-睾酮和雄激素-比卡鲁胺复合物中观察到的相互作用模式，利用了共结晶配体用于结合的65%至83%的氨基酸残基。这项计算研究表明，一些PCDF同系物可能通过与受体的不适当结合，在人类和野生动物中充当雄激素受体的激动剂和拮抗剂。
