Methoxylated flavonols from Seub ethyl acetate active myeloperoxidase extract: in vitro and in silico assays.

This study aimed to evaluate the effect of a methoxylated fraction from Seub on myeloperoxidase (MPO)-chlorinating activity and subsequent assays for binding profile prediction. Therefore, the ethyl acetate extract of aerial parts from Seub was fractionated on open-column chromatography containing SiO and eluted with solvent in crescent polarity to yield a fraction with a mixture of flavonols quercetin 3--methyl ether () and 6-C-methyl quercetin 3--methyl ether (). Their chemical structures were proposed by HPLC coupled to photodiode array (HPLC-DAD) and mass spectrometer using electrospray ionization multistage analysis (HPLC-MS/MS). The fraction enriched with compounds and inhibited more efficiently the MPO-chlorinating activity (IC = 40 µg/mL) than the ethyl acetate extract (IC = 64.0 µg/mL). Molecular docking studies revealed that these compounds interact with MPO active pocket similarly to trifluoromethyl-substituted aromatic hydroxamate, a well-known MPO inhibitor, co-crystallized at the MPO binding site (PDB ID: 4C1M). Molecular dynamics trajectories confirmed that these two molecules interact with the MPO binding site with a similar energetic pattern when compared to the crystallographic ligand. Taken together, these data expand the sources of phenolic natural compounds that may be further investigated against inflammation-related diseases. Communicated by Ramaswamy H. Sarma.