Novel potent natural peroxidases inhibitors with in vitro assays, inhibition mechanism and molecular docking of phenolic compounds and alkaloids.

Peroxidase inhibition produced by phenolic compounds as hispidin and gallic acid, alkaloids as harmine and natural extracts of Inonotus hispidus, and Marrubium vulgare were investigated in this study. No further studies have been found in this context. Thus, the results show that the phenolic and the alkaloidal extracts with the three molecules are potent inhibitors of horseradish peroxidase. Uric acid is used as a substrate reaction to finding the enzymatic inhibition for the first time. The results show that the best inhibitor is hispidin with a value of IC50 = 23 µg/ml. Moreover, Molecular docking has been carried out using the AutoDock Vina program to discuss the nature of interactions and the mechanism of inhibition between both peroxidases (horseradish and thyroid) which is performed with and without heme group for the first time. The three studied compounds were further subjected to ADEMT and Lipinski filtering analyses for drug-likeness prediction analysis. However, the results show that all the docked molecules are competitive inhibitors confirming that no further studies have been published before. Thus, hispidin is a more potent irreversible TPO inhibitor then propylthiouracil anti-thyroid drug. Its inhibition mechanism is well described through this work for the first time; which suggests is used as an anti-thyroid drug to treat hyperthyroidism. Furthermore, the studied phenolic compounds (Hispidin and Gallic acid) and one alkaloid (Harmine) are non-toxic, that bind to the receptor-binding site and catalytic dyad of peroxidases were identified from the predictive ADMET and Lipinski filter analysis. Communicated by Ramaswamy H. Sarma.