Methoxylated flavonols from Vellozia dasypus 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 Vellozia dasypus Seub on myeloperoxidase (MPO)-chlorinating activity and subsequent in silico assays for binding profile prediction. Therefore, the ethyl acetate extract of aerial parts from Vellozia dasypus 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-O-methyl ether (1) and 6-C-methyl quercetin 3-O-methyl ether (2). 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 1 and 2 inhibited more efficiently the in vitro 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

Keywords:

• Myeloperoxidase
• Vellozia dasypus
• flavonoids
• molecular modeling

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This study was supported by grants from “Fundação de Amparo à Pesquisa do Estado da Bahia” (FAPESB) (RED038/2014; APP0029/2016; DTE17/2015) and “Conselho Nacional de Desenvolvimento Científico Tecnológico” (CNPq) (462401/2014-6). AB is a CNPq fellow researcher (grant 307996/2018-2).