Hop plants comprise a variety of natural compounds greatly differing in their structure and properties. A wide range of methods have been developed for their isolation and chemical analysis, as well as for determining their antioxidative, antimicrobial, and antigenotoxic potentials. This contribution provides an overview of extraction and fractionation techniques of the most important hop compounds known for their health-promoting features. Although hops remain the principal ingredient for providing the taste, stability, and antimicrobial protection of beer, they have found applications in the pharmaceutical and other food industries as well. This review focuses on numerous health-promoting effects of hops raging from antioxidative, sedative, and anti-inflammatory potentials, over anticarcinogenic features to estrogenic activity. Therefore, hops should be exploited for the prevention and even healing of several prevalent diseases like cardiovascular disorders and various cancer types. New ideas for future studies on hops are finally presented: computational investigations of chemical reactivities of hop compounds, nanoencapsulation, and synergistic effects leading to a higher bioavailability of biologically active substances as well as the application of waste hop biomass from breweries for the production of high-added-value products in accordance with the biorefinery concept.

Acrylonitrile (AN) is widely used in the manufacture of resins, plastics, and polymers, where workers are exposed to it during its production, transportation, and application. After intake a portion of AN is converted to cyanoethylene oxide (CEO) by cytochrome P450 2E1. Both AN and CEO represent possible chemical carcinogens leading to DNA damage mainly in the form of the major 7-(2-oxoethyl)deoxyguanosine adduct. A kinetic model for its formation was devised and a corresponding second-order rate constant obtained from the experimental data on the reaction with CEO. A series of ab initio, density functional theory, and semiempirical calculations of activation free energies was then performed on the alkylation of nucleic bases with both CEO and AN. The combination of Hartree-Fock level of theory with the flexible 6-311++G(d,p) basis set and Langevin dipoles implicit solvation model gave the best agreement with the experimental activation barrier. It also predicted relative reactivities of all four nucleobases that are in agreement with the experimentally reported adduct yields. Moreover, this combination predicted higher reactivity of CEO than AN with all four nucleobases corroborating the experimental hypothesis that S2 substitution of CEO rather than direct Michael addition of AN is responsible for the genotoxic properties of AN. In a broader context this paper points to the applicability of quantum chemical methods to the studies of carcinogenesis.

The discovery that β-propiolactone (BPL), once a commercially important chemical, causes various tumors in experimental animals has led to a significant decrease in its use. However, owing to its efficacy this possible human carcinogen remains to be utilized in vaccines for inactivation of viruses. The focus of the current study was to uncover the mechanisms of β-propiolactone reactions with both nucleobases and glutathione (GSH) through computer simulations based on quantum chemical methods. Our results, in accordance with in vitro studies, show that among all nucleobases guanine most readily forms adducts with BPL through SN2 reaction mechanism. Acquired activation energies with incorporated solvent effects reveal that alkylation represents an energetically more favorable reaction than acylation for all nucleobases. Comparison of activation free energies of glutathione and guanine reactions with BPL suggest that glutathione may represent an efficient natural scavenger of BPL. Therefore, glutathione present in the organism may provide protection to the DNA and thus prevent BPL’s genotoxicity, mutagenicity, and possibly even carcinogenicity.

Our study aims to investigate the impact of the Maturity-onset diabetes of the young 3 disease-linked rSNP rs35126805 located in the HNF-1α gene promotor on the binding of the transcription factor HNF-4α and consequently on the regulation of HNF-1α gene expression. Our focus is to calculate the change in the binding affinity of the transcription factor HNF-4α to the DNA, caused by the regulatory single nucleotide polymorphism (rSNP) through molecular dynamics simulations and thermodynamic analysis of acquired results. Both root-mean-square difference (RMSD) and the relative binding free energy ΔΔGbind reveal that the HNF-4α binds slightly more strongly to the DNA containing the mutation (rSNP) making the complex more stable/rigid, and thereby influencing the expression of the HNF-1α gene. The resulting disruption of the HNF-4α/HNF-1α pathway is also linked to hepatocellular carcinoma metastasis and enhanced apoptosis in pancreatic cancer cells. To the best of our knowledge, this represents the first study where thermodynamic analysis of the results obtained from molecular dynamics simulations is performed to uncover the influence of rSNP on the protein binding to DNA. Therefore, our approach can be generally applied for studying the impact of regulatory single nucleotide polymorphisms on the binding of transcription factors to the DNA.