Computational investigation of Crateva religiosa bark phytoconstituents as potential modulators of Hyperthyroidism

Abstract Crateva religiosa possesses a diverse array of biologically and pharmacologically active phytoconstituents in its bark, including stigmasterol, β-k-strophanthin, drebyssogenin, β-sitosterol, lupeol, and giganteumgenin. These natural compounds are traditionally known for their therapeutic potential, including in managing hyperthyroid conditions. In this study, an in silico molecular docking approach was employed to investigate the binding affinities of major bark phytoconstituents of Crateva religiosa with key hyperthyroidism-related targets: myeloperoxidase (MPO, PDB: 1CXP), thyroid hormone receptors α and β (HTR-α, PDB: INAV; HTR-β, PDB: 1N46), and BDR-4 (PDB: 3MXF). Docking was conducted using AutoDock Tools 4.2.1, evaluating dock scores for each ligand-protein interaction. The results revealed that β-sitosterol and stigmasterol exhibited the most favorable binding affinities, with docking energies as low as − 9.29 and − 7.00 kcal/mol, respectively, against HTR-α, HTR-β, and BDR-4. Lepuol exhibit with − 7.12 kcal/mol binding affinity towards MPO target. Drebyssogenin also showed notable affinity towards HTR-α (–9.06 kcal/mol). The standard reference inhibitor, methimazole, showed significantly interaction profiles (–3.37 to − 3.55 kcal/mol) across all targets. These findings highlight β-sitosterol and stigmasterol as promising phytoconstituent leads for further antithyroid drug development. The noticeable binding efficiency of these compounds suggests their potential as selective thyroid hormone receptor modulators and warrants subsequent experimental validation for therapeutic application in hyperthyroidism management. Graphical Abstract