Methoxylated flavonols from <i>Vellozia dasypus</i> Seub ethyl acetate active myeloperoxidase extract: in vitro and in silico assays

Abstract

This study aimed to evaluate the effect of a methoxylated fraction from <i>Vellozia dasypus</i> Seub on myeloperoxidase (MPO)-chlorinating activity and subsequent <i>in silico</i> assays for binding profile prediction. Therefore, the ethyl acetate extract of aerial parts from <i>Vellozia dasypus</i> Seub was fractionated on open-column chromatography containing SiO₂ and eluted with solvent in crescent polarity to yield a fraction with a mixture of flavonols quercetin 3-<i>O</i>-methyl ether (<b>1</b>) and 6-C-methyl quercetin 3-<i>O</i>-methyl ether (<b>2</b>). 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 <b>1</b> and <b>2</b> inhibited more efficiently the <i>in vitro</i> MPO-chlorinating activity (IC₅₀ = 40 µg/mL) than the ethyl acetate extract (IC₅₀ = 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.