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

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.

Hyptis verticillata; Hyperthyroidism; Thyroid peroxidase; Molecular docking; In silico analysis; ADMET; Natural TPO inhibitors; Phytochemicals

1. Akinola, A. M., Dearsly, E. M., Ikegima, E., Eze, K. C., Patrick, O. N., Mmadu, M. E., Dada, E. D., & Anwanabasi, I. O. (2025). Structure-Based Investigation of Chromolaena odorata Compounds Against Key Proteins Implicated in Obesity Using Molecular Docking Approaches. International Journal of Research and Innovation in Applied Science, X(VII), 928–945. https://doi.org/10.51584/ijrias.2025.100700084 [Google Scholar] [Crossref]

2. Awad, S. M., El-Shafey, M. Y., Hegazy, M. E. F., Abdelwahab, O., & Mohamed, A. A. (2018). Design, synthesis, molecular modeling, and biological evaluation of novel thiouracil derivatives as thyroid peroxidase inhibitors. Molecules, 23(11), 2913. [Google Scholar] [Crossref]

3. Chaudhary, S., Dixit, A., & Bist, P. (2022). Hyperthyroidism: An overview of etiology, clinical features, diagnosis and management. Journal of Clinical and Diagnostic Research, 16(2), OE01–OE06. [Google Scholar] [Crossref]

4. Dearsly, E. M., Dada, E. D., Olukayode, O., Eze, K. C., Rhema, M. E., Adaeze, C. C., Ikegima, E., & Shaibu, A. O. (2025). Pharmacokinetic studies and molecular docking studies of the Anti-Ulcer potential of Musa sapientum phytocompunds. International Journal of Research and Innovation in Applied Science, X(VII), 790–803. https://doi.org/10.51584/ijrias.2025.100700071 [Google Scholar] [Crossref]

5. Dearsly, E. M., Olukayode, O., Ojoma, A. P., Dada, E. D., Eze, K. C., Igiakong, G. P., & Ogidigo, J. C. (2025). Aframomum Danielli Phytocompounds as promising inhibitors of salmonella Typhi targets: An in silico approach. International Journal of Research and Innovation in Applied Science, X(VI), 926–938. https://doi.org/10.51584/ijrias.2025.10060069 [Google Scholar] [Crossref]

6. Habza-Kowalska, E., Wysocka, A., Kosmalska, M., & Krzemiński, P. (2019). Thyroid peroxidase activity is inhibited by phenolic compounds: Insights into mechanisms. International Journal of Molecular Sciences, 20(23), 6119. [Google Scholar] [Crossref]

7. Kuhnt, M., Pröbstle, A., Rimpler, H., Bauer, R., & Heinrich, M. (1995). Biological and pharmacological activities and further constituents of Hyptis verticillata. Planta Medica, 61(3), 227–232. [Google Scholar] [Crossref]

8. Morris, G. M., & Lim-Wilby, M. (2008). Molecular docking. In Molecular Modeling of Proteins (pp. 365–382). Humana Press. [Google Scholar] [Crossref]

9. Pérez, J. L., Alfonso, D., & Rivera, M. (2020). Chemical constituents and pharmacological properties of Hyptis verticillata. Journal of Medicinal Plants Research, 14(8), 443–450. [Google Scholar] [Crossref]

10. Picking, D., Delgoda, R., Boulogne, I., & Mitchell, S. (2013). Hyptis verticillata Jacq: A review of its traditional uses, phytochemistry, pharmacology and toxicology. Journal of Ethnopharmacology, 150(1), 14–33. [Google Scholar] [Crossref]

11. Rivera, M., Rodríguez, A., & Blanco, D. (2019). Therapeutic applications of Hyptis verticillata: A systematic review. Phytomedicine, 62, 152959. [Google Scholar] [Crossref]

12. Suryandari, D. A., Zahroh, H., Suhartati, R., & Martosupono, M. (2020). Molecular insights into propylthiouracil as a thyroid peroxidase inhibitor. International Journal of Molecular and Cellular Medicine, 9(2), 97–109. [Google Scholar] [Crossref]

13. Taurog, A. (2013). Thyroid peroxidase and thyroid hormone synthesis. In L. E. Braverman & D. S. Cooper (Eds.), Werner & Ingbar’s The Thyroid: A Fundamental and Clinical Text (10th ed., pp. 48–73). Lippincott Williams & Wilkins. [Google Scholar] [Crossref]

14. Yadav, P., Suri, S., Singh, G., & Gupta, S. (2021). Comparative evaluation of antithyroid drugs: Clinical efficacy and safety profiles. Endocrine Reviews, 42(3), 365–389. [Google Scholar] [Crossref]

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