An experimental and theoretical study of ROS scavenging by organosulfur compounds from garlic: In silico analysis of metabolic pathways and interactions on CYP2E1

DIAZ, MARIO GUILLERMO; FERRARI, GABRIELA VERONICA; ANDRADA, MATÍAS FERNANDO; VEGA-HISSI, ESTEBAN; MONTAÑA, MARIA PAULINA; MARTINEZ, JUAN CEFERINO GARRO

JOURNAL OF SULFUR CHEMISTRY

TAYLOR & FRANCIS LTD

Año: 2022 vol. 43 p. 620 - 642

1741-5993

Using experimental and computational methodologies, we analyzed the possible interactions of two organosulfur compounds (OSC), Allyl methyl sulfide (AMS) and Diallyl sulfide (DAS), with different reactive oxygen species (ROS), which cause oxidative stress. Additionally, we study both OSC as inhibitors of CYP2E1, an enzyme involved in the generation of ROS. Effective quantitative interaction of both OSC with H2O2, O2• - and O2(1Δg) was found by experimental methods. The experimental k values at 288 K of H2O2 scavenging reaction for AMS (5.43 × 10−20 cm3 molecule−1 s−1) and DAS (1.65 × 10−21 cm3 molecule−1 s−1) indicate the reaction is more quick when AMS is the reactant. This trend was maintained when the HO• scavenging reactions were analyzed with computational methodologies using IRC calculations with M06-2x/6-311++G(3df, 2p) level of theory and gaseous, aqueous and no-polar phases. An in silico analysis of OSC and their metabolites derived from epoxidation and sulfoxidation reactions showed that these compounds present a high probability of being inhibitors of the CYP2E1 enzyme. The molecular docking showed an effective binding in the complexes enzyme-OSC and enzyme-metabolites, with a major interaction between the sulfur and oxygen atoms and the heme iron ion.