Molecular interactions of chlorpyrifos and its environmental degradation products with human sex hormone-binding globulin: an in silico study.

Abstract

In recent years, there has been a widespread interest and awareness about health issues posed by endocrine-disrupting chemicals present in the environment. These chemicals, often present in food and many consumer products, can interfere with hormone biosynthesis and metabolism and may result in deviation from normal homeostatic control. Chlorpyrifos (CPF), a major endocrine-disrupting chemical is used worldwide as an agricultural insecticide against a broad spectrum of insect pests in rice cultivation and to control termites. The insecticide mostly undergoes environmental degradation to chlorpyrifos-oxon (CPYO), des-ethyl chlorpyrifos (DEC), 3,5,6-trichloro-2-methoxypyridine (TMP) and 3,5,6-trichloro-2-pyridinol (TCP). Results from several epidemiological studies suggest that exposure to CPF can result in reproductive disorders, including infertility in male and female. Sex hormone-binding globulin (SHBG) is a circulatory protein that binds sex steroids and is a potential target for endocrine disruptors in the human body. The objective of the present study involved computational approaches to apprehend the mechanism of molecular interaction of CPF and its four degradation products (CPYO, DEC, TMP, TCP) with human SHBG using molecular docking simulation. All five compounds (CPF, CPYO, DEC, TMP, TCP) showed high binding affinity with SHBG; however, the binding affinity values were higher (more negative) for CPF, CPYO, DEC and TMP than for TCP indicating that CPF, CPYO, DEC and TMP formed a tight interaction with SHBG. From the results obtained with the docking analysis, it can be opined that CPF, CPYO, DEC and TMP could possibly act as potential endocrine disruptors for androgen signaling.