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

MARIO DIAZ; GABRIELA FERRARI; ESTEBAN G. VEGA-HISSI; ANDRADA MATIAS; PAULINA MOTAÑA ; GARRO MARTINEZ JUAN C

JOURNAL OF SULFUR CHEMISTRY

TAYLOR & FRANCIS LTD

Lugar: Londres; Año: 2022

1741-5993

Using experimental and computational methodologies, we performed a complete analysis of the possible interaction of two organosulfur compounds (OSC), Allyl methyl sulfide (AMS) and Diallyl sulfide (DAS) with different reactive oxygen species (ROS) which are causing oxidative stress. Additionally, we study both OSC as inhibitors of CYP2E1, an enzyme involved in the generation of ROS. An 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 quickly when AMS is the reactant. This trend is 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 three different environments: 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 high probability to be inhibitors of CYP2E1 enzyme. The molecular docking showed an effective binding in the complexes enzyme-OSC and enzyme-metabolites, with an important interaction between the sulfur and oxygen atoms and the heme iron ion.