DESIGNING NATURAL AGONISTS FOR THYROID HORMONE RECEPTOR ALFA-1

Hypothyroidism is a common disorder of endocrine system in which the thyroid gland does not produce enough thyroid hormone. The most common cause of hypothyroidism is inflammation of the thyroid gland, which damages the gland’s cells. It can affect growth, cellular processes and many other body functions. As more damage accumulates, the risk of Hypothyroidism increases. In order to make an impact on Hypothyroidism, we must understand the molecular processes and structure-function relationships of TSH permitted better understanding of the role of specific protein and carbohydrate domains in the synthesis, bioactivity, and clearance of this hormone. Thyroid hormone receptor alfa-1 (THRA1) is an endocrine nuclear receptor that mediates the transcriptional effects of thyroid hormone (triiodothyronine, T₃). It acts as an agonist i.e. it stimulates the production of thyroid hormone by triggering a response in the cell, which is selected as target protein. The primary goal of the project was to unearth natural chemical compounds that can be used as an agonist (increase thyroid hormone level in patients) for the treatment of hypothyroidism. The most effective compounds were isolated from Ashvagandha (Withania somnifera). A total of 14 molecules were selected. The molecules were screened based on the Lipinski’s rule of 5. The screened molecules were subjected to toxicity analysis and those that passed the toxicity tests were analyzed for energy minimization and docking studies. From the docking studies analysis it was found that 5 compounds (Pseudotropine, Somniferinine, Withanolide -A, Withanolide – D and Withanine) were the lead compound for the hypothyroidism. Amongst these 5 Withanolide_D gave the best results.