AN ALTERNATIVE TO ENDOSULFAN: STRUCTURE BASED PHARMACOPHORE MODELING, GLIDE AND MM-GBSA ANALYSIS OF ECDYSONE RECEPTOR AND MOLECULAR DYNAMICS STUDIES

Endosulfan, an insecticide which is considered as a boon to farmers to control, a host of insects that are responsible for various diseases in plants on the other hand has lethal effects on human beings as it is a carcinogen. The target of endosulfan in all the arthropods is the Ecdysone receptor which is homologous to the human Estrogen Receptor. As endosulfan is an Estrogen like endocrine disrupting chemical, it mimics estrogen and binds to the estrogen receptors causing various disorders like breast cancer and other disorders related to attainment of puberty. Phytochemical compounds tend to bind to the ER beta receptor which doesn’t affect the estrogen binding. A pharmacophore was developed keeping in mind, the binding pattern of flexible endosulfan with the flexible Ecdysone receptor. The developed pharmacophore was used to screen the database of phytochemical compounds to identify the hits. These hits were docked with the Ecdysone receptor and were shortlisted based on three criteria: i) glide score ii) active site residues interactions with ecdysone receptor and iii) binding free energy. Interestingly, one of the obtained compounds named Brassinolide, was known to have insecticidal activity indicating that the developed pharmacophore model would be useful for identifying s insecticides.