INVESTIGADORES
ANDRADA Matias Fernando
congresos y reuniones científicas
Título:
HYPOCHLOROUS ACID SCAVENGER ACTIVITY OF NITRONES: AN EXPERIMENTAL AND THEORETICAL STUDY
Autor/es:
DIMARCO, FRIDA; DIAZ, MARIO GUILLERMO; VEGA-HISSI ESTEBAN; ANDRADA, MATIAS F.; GOMEZ MEJIBA SE; RAMIREZ, DARIO; GARRO MARTINEZ JUAN
Lugar:
San Juan, Argentina
Reunión:
Encuentro; 40) XLI Reunión Científica Anual de la Sociedad de Biología de Cuyo; 2023
Institución organizadora:
Sociedad de Biología de Cuyo
Resumen:
Hypochlorous acid (HOCl) is a hydrohalogenated reactive oxygen species (ROS) that is produced in living organisms,in the presence of hydrogen peroxide (H2O2). When HOCl is produced in excessive amounts, it can oxidize the body'sown biomolecules such as proteins, lipids, and nucleic acids, leading to tissue damage and the appearance of certaincardiovascular and neurodegenerative diseases in addition to others such as atherosclerosis, arthritis, and cancer. Agroup of organic molecules called nitrones is of interest in this field because they are capable of acting as ROSscavengers. Chemically, nitrones are N-oxides of imines with a general molecular structure of the type R1R2C=N+-O- R3(where R1, R2 and R3 = an alkyl group, and R1 or R2=H). The nitrone functional group (C=N+-O-) is formed by threeatoms that share four π electrons. This specific structure is responsible for the reactivity, turning these molecules into74organic compounds effective against different oxidizing species and free radicals. The objective of this research is todetermine the HOCl scavenger activity of six of nitrones, which contain in their structure a substituted five-memberedring (furan or thiophene), and to explain the experimental activity using computational methods. Experimentally, fournitrones showed HOCl scavenging activity with IC50 values ranging from 26.15 to 61.20 nM, while two nitrones wereinactive. To explain their activity, a reaction mechanism based on a nucleophilic attack of the hypochlorous anion(pKa=7.46) on the α-carbon of each nitrone was proposed using DFT calculations. In addition, the rate constants (k),HOMO and LUMO energies, and various reactivity indices such as electronic chemical potential (μ), chemical hardness(η), and overall electrophilicity (ω) were calculated. We found that the rate constants and the global electrophilicityshow a high correlation with the activity. Concurrently, we performed a SAR analysis to elucidate the influence of thesubstituents presented in the six nitrones.