HR‐MS Analysis of the Covalent Binding of Edaravone to 5‐Formylpyrimidine Bases and a DNA Oligonucleotide Containing a 5‐Formylcytidine Residue

Rapid Communications in Mass Spectrometry, Journal Year: 2025, Volume and Issue: 39(14)

Published: April 21, 2025

ABSTRACT Rationale Edaravone (EDA) is a radical scavenger and an antioxidant drug approved to treat amyotrophic lateral sclerosis used as research tool explore treatment of neurodegenerative diseases cancers. It also reactive agent, known PMP (1‐phenyl‐3‐methyl‐5‐pyrazolone), for the analysis polysaccharides composition. EDA can react with sugars aromatic aldehydes. In this context, we have investigated reactivity toward biologically relevant formylated nucleobases, nucleosides, oligonucleotide containing residue. Methods The formation both mono‐ bis‐adducts between nucleobases (5‐formyluracil (5fU) 5‐formylcytosine (5fC)) or corresponding nucleosides 5‐fdU 5‐fdC was characterized using high‐resolution mass spectrometry (HR‐MS). Similarly, covalent binding 8‐mer palindromic d (TATG[*C]ATA) single residue [*C] under physiological conditions spectrometry. Results For first time, shown pyrimidines. Covalent stable adducts were identified. found efficiently generate bis‐adducts. rate mono‐adduct five times higher than that bis‐adduct. reaction aldehydic DNA modifications such 5fU/5fC may important consequences in terms gene expression. Conclusions These observations raise implications epigenetic contribution mechanism action EDA. biological our vitro results are discussed, notably frame

Language: Английский

Synthesis, Characterization and Assessment of Antioxidant and Melanogenic Inhibitory Properties of Edaravone Derivatives

Antioxidants, Journal Year: 2024, Volume and Issue: 13(9), P. 1148 - 1148

Published: Sept. 23, 2024

A series of edaravone derivatives and the corresponding Cu(II) complexes were synthesized characterized using spectroscopic analytical techniques such as IR, UV, NMR elemental analysis. Antioxidant activities all compounds examined free radical scavenging methods hydrogen peroxide activity (HPSA), 1,1-diphenyl-2-picrylhydrazyl (DPPH) 2-2′-azino-bis-(3-ethylbenzothiazoline-6-sulfonate) (ABTS) assays. All tested exhibited good antioxidant activity. Further, frontier orbital energy levels, well various chemical properties, determined density functional theory (DFT) calculations. The MEP maps plotted to identify nucleophilic electrophilic reactive sites. binding energies organic with protein tyrosinase was investigated determine their potential anti-melanogenic applications. selected ligand, L6 subjected molecular dynamics simulation analysis stability ligand–protein complex. MD performed (150 ns) estimate tyrosinase–L6 Other key parameters, as, RMSD, RMSF, Rg, bonds, SASA MMPBSA also analyzed understand interaction protein.

Language: Английский