Molecular docking study and ADMET prediction of the effects of some food alkaloids on thyroxine homeostasis through their interactions with human thyroxine-binding globulin.

Abstract

Thyroid hormones (THs) play a vital role in several physiological functions of the body. At the circulatory level, thyroxine (T4) has been found to be the predominant form of THs. The distribution of T4 in the blood is mainly carried out by human thyroxine-binding globulin (hTBG). This process can be interfered with by various natural substances present in foods, particularly alkaloids. Some of these alkaloids have been shown to possess a cyclic chemical structure similar to that of T4. It has therefore been hypothesised that this class could potentially compete with T4 transport in the bloodstream. A molecular docking study and ADMET prediction were performed with ten selected food alkaloids. Predicted ADMET analysis revealed that all compounds tested had adequate solubility, high human gastrointestinal absorption and minimal risk of hepatotoxicity and cardiotoxicity. Molecular docking data showed that piperine, nigellidine, capsaicin, nigellicine, and 3-hydroxyquinine had a high affinity for hTBG, with respective binding energies of - 8.1, - 8.0, - 7.7, - 7.2 and - 7.1 kcal/mol. This finding indicates that these alkaloids were successfully positioned in the binding site of hTBG and had the ability to compete with T4 and increase its free level in the bloodstream. Therefore, two suggestions can be withdrawn, depending on the physiological state of the thyroid gland. Overconsumption of these alkaloids may lead to an imbalance in T4 homeostasis in both healthy individuals and hyperthyroid patients. Conversely, this competitive dynamic may offer a therapeutic advantage in the management of hypothyroidism.