Screening of in Vitro Inhibition of Lactoperoxidase Enzyme by Methyl Benzoate Derivatives with Molecular Docking Studies

Abstract

AbstractLactoperoxidase enzyme (LPO) is secreted from salivary, mammary, and other mucosal glands including the bronchi, lungs, and nose, which had functions as a natural and the first line of defense towards viruses and bacteria. In this study, methyl benzoates were examined in LPO enzyme activity. Methyl benzoates are used as precursors in the synthesis of aminobenzohydrazides used as LPO inhibitors. For this purpose, LPO was purified in a single step using sepharose‐4B‐l‐tyrosine‐sulfanilamide affinity gel chromatography with a yield of 9.91 % from cow milk. Also, some inhibition parameters including the half maximal inhibitory concentration (IC50) value and an inhibition constant (Ki) values of methyl benzoates were determined. These compounds inhibited LPO with Ki values ranging from 0.033±0.004 to 1540.011±460.020 μM. Compound 1 a (methyl 2‐amino‐3‐bromobenzoate) showed the best inhibition (Ki=0.033±0.004 μM). The most potent inhibitor (1 a) showed with a docking score of −3.36 kcal/mol and an MM‐GBSA value of −25.05 kcal/mol, of these methyl benzoate derivatives (1 a–16 a) series are established H‐bond within the binding cavity with residues Asp108 (distance of 1.79 Å), Ala114 (distance of 2.64 Å), and His351 (distance of 2.12 Å).