“In Silico Docking Analysis of phytocompounds as Potential Inhibitors of Thyroid Peroxidase (TPO) in the Management of Hyperthyroidism”

Abstract

Hyperthyroidism is a metabolic disorder characterized by excessive synthesis of thyroid hormones, primarily mediated by thyroid peroxidase (TPO), a key enzyme involved in iodination and coupling reactions during hormone biosynthesis. Conventional antithyroid drugs target TPO but are often associated with adverse effects, prompting the search for safer, plant-derived alternatives. This study employed an in silico approach to investigate the inhibitory potential of bioactive compounds from Hyptis verticillata against human thyroid peroxidase. Selected phytochemicals were retrieved from public databases and subjected to molecular docking using AutoDock Vina integrated within PyRx. Drug-likeness properties were evaluated using Lipinski, Ghose, Veber, Egan, and Muegge rules, while pharmacokinetic and toxicity profiles were predicted via SwissADME and pkCSM. Docking analysis revealed binding affinities ranging from −3.8 to −5.5 kcal/mol, with squalene (−5.5 kcal/mol), R-R,R-E-trans-phytol (−5.3 kcal/mol), and 3a,4,5,6,7,7a-hexahydro-4,7-methanoindene (−5.0 kcal/mol) exhibiting the strongest interactions within the TPO active site. These compounds formed stable hydrophobic interactions that may hinder substrate access to the catalytic center of the enzyme. ADMET predictions indicated favorable gastrointestinal absorption, low toxicity, and acceptable pharmacokinetic profiles for the top-ranking compounds. Overall, the findings suggest that Hyptis verticillata contains phytochemicals with promising TPO inhibitory potential, providing a molecular basis for its traditional use and supporting further experimental validation for hyperthyroidism management.