3D QSAR studies of hydroxylated polychlorinated biphenyls as potential xenoestrogens
| Autor: | Kundan Ingale, Moiz Mumtaz, John S. Wheeler, Patricia Ruiz |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Quantitative structure–activity relationship Environmental Engineering Stereochemistry Health Toxicology and Mutagenesis In silico Estrogen receptor Quantitative Structure-Activity Relationship Saccharomyces cerevisiae 010501 environmental sciences Hydroxylation Ligands 01 natural sciences Molecular Docking Simulation Article Xenobiotics 03 medical and health sciences chemistry.chemical_compound Genes Reporter Two-Hybrid System Techniques Environmental Chemistry Organic chemistry Humans Computer Simulation Estrogens Non-Steroidal Databases Protein 0105 earth and related environmental sciences Biphenyl Binding Sites Public Health Environmental and Occupational Health Estrogen Receptor alpha Hydrogen Bonding General Medicine General Chemistry Pollution Polychlorinated Biphenyls 030104 developmental biology chemistry Docking (molecular) Estrogen receptor alpha Protein Binding |
| Zdroj: | Chemosphere |
| Popis: | Mono-hydroxylated polychlorinated biphenyls (OH-PCBs) are found in human biological samples and lack of data on their potential estrogenic activity has been a source of concern. We have extended our previous in silico 2D QSAR study through the application of advance techniques such as docking and 3D QSAR to gain insights into their estrogen receptor (ERα) binding. The results support our earlier findings that the hydroxyl group is the most important feature on the compounds; its position, orientation and surroundings in the structure are influential for the binding of OH-PCBs to ERα. This study has also revealed the following additional interactions that influence estrogenicity of these chemicals (a) the aromatic interactions of the biphenyl moieties with the receptor, (b) hydrogen bonding interactions of the p-hydroxyl group with key amino acids ARG394 and GLU353, (c) low or no electronegative substitution at para-positions of the p-hydroxyl group, (d) enhanced electrostatic interactions at the meta position on the B ring, and (e) co-planarity of the hydroxyl group on the A ring. In combination the 2D and 3D QSAR approaches have led us to the support conclusion that the hydroxyl group is the most important feature on the OH-PCB influencing the binding to estrogen receptors, and have enhanced our understanding of the mechanistic details of estrogenicity of this class of chemicals. Such in silico computational methods could serve as useful tools in risk assessment of chemicals. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|