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

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, O-2(center dot -) and O-2((1)Delta(g)) was found by experimental methods. The experimental k values at 288 K of H2O2 scavenging reaction for AMS (5.43 x 10(-20) cm(3) molecule(-1) s(-1)) and DAS (1.65 x 10(-21) cm(3) molecule(-1) s(-1)) indicate the reaction is more quick when AMS is the reactant. This trend was maintained when the HO center dot 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.