Pharmacology and Toxicology

Cancer is a major cause of death in developed countries, second aft er cardiac disease. In most of the cases, carcinogenesis is associated with chemical modifi cation of DNA. Th erefore, exogenous chemical carcinogens are indeed implicated in the aetiology of an increasing number of cancer types. Th e focus of the current contribution was to examine [6]-gingerol from ginger as a natural scavenger of nine ultimate chemical carcinogens: afl atoxin B1 exo-8,9-epoxide, β-propiolactone, 2-cyanoethylene oxide, ethylene oxide, chloroethylene oxide, glycidamide, propylene oxide, styrene oxide and vinyl carbamate epoxide. To evaluate [6]-gingerol effi ciency, we expanded our research with an examination of glutathione - the strongest endogenous scavenger of chemical carcinogens in human cells. Ab initio calculations of activation free energies were performed at the Hartree-Fock level of theory in conjunction with three fl exible basis sets. Our results obtained with implicit solvation imply that glutathione cannot effi ciently protect us from all studied chemical carcinogens, meaning that additional protection is required for prevention of chemical carcinogenesis. According to our results, [6]-gingerol proved to be a universal and extremely effi cient natural scavenger of all chemical carcinogens of the epoxy type. Th erefore, additional protection could

be assured by [6]-gingerol prophylaxis. Moreover, the obtained results present strong evidence in favor of the validity of the proposed SN2 reaction mechanism for the alkylation reactions of [6]-gingerol and glutathione with chemical carcinogens of the epoxy type and point to the applicability of quantum chemical methods to studies of early chemical carcinogenesis. Th e results of our study identifi ed a novel natural scavenger, namely [6]-gingerol, that could effi ciently prevent DNA alkylation damage by covalently binding to all studied ultimate carcinogens via a lower activation barrier. Th erefore, we strongly believe that this research represents the basis for further computational, experimental and clinical studies of anti-carcinogenic properties of [6]-gingerol and for development of novel selective dietary supplements.