Identification of bioactive agents from green onion (Allium spp.) and organoselenium compounds with cancer chemopreventive potential

Alliums have been long associated with a battery of health benefits. This dissertation was carried out with the goal of identifying potential cancer chemopreventive agents from green onion (Allium spp.) and related compounds using Phase II enzyme induction and antioxidant properties as primary and secondary biomarkers, respectively.; Relative to standard antioxidants (ascorbic acid, n-propyl gallate, butylated hydroxytoluene, Trolox, and reduced glutathione), pure thiosulfinates, R-S(O)S-R, where R = methyl, propyl or allyl, were 1--3 orders of magnitude less efficient at reducing 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, 0.5--2 orders of magnitude less efficient at quenching singlet oxygen, and about equally effective at scavenging hydroxyl radical. None of these thiosulfinates at levels up to 4 mM demonstrated any hydrogen peroxide or superoxide anion scavenging effects. These thiosulfinates were also incapable at levels up to 0.1 mM (where they were toxic) of in vitro induction of quinone reductase (QR) in murine hepatoma (Hepa 1c1c7) cells.; Twenty-seven selenium compounds as well as sixteen structurally related organosulfur compounds were tested for QR and glutathione-S-transferase (GST) activity in Hepa 1c1c7 cells. Sixteen selenium compounds were able to double QR activity, and seven of them also doubled GST activity. Nine compounds, including dimethyl diselenide (DMDSe), 2,5-diphenyl-selenophene, dibenzyl diselenide, methylseleninic acid (MSeA), diphenyl diselenide, benzeneseleninic acid, benzene selenol, triphenylselenonium chloride and ebselen, were shown to be potent Phase II enzyme inducers with CD values (for QR) lower than 7 muM.; Freeze-dried green onion was subject to QR-induction bioassay guided fractionation. Crude solvent extracts (both non-polar and polar) were prepared from green onion tissue by sequential refluxing with hexane, ethyl acetate and then methanol, followed by liquid-liquid extraction. Active fractions were subjected to flash chromatography, thin layer chromatography (TLC) and high pressure preparative liquid chromatography (HPLC) to afford pure isolates capable of inducing QR. Multiple fractions were active in inducing QR. Ten pure compounds were isolated from active fractions and identified using spectroscopic methods, and they were 5,6-dimethyl-2-pyridinecarboxylic acid, ferulic acid, 1-(6-hydroxy-[3]pyridyl)-propan-1-one, N-trans-feruloyl 3- O-methyldopamine, 5-(hydroxymethyl) furfural, acetovanillone, 5-hydroxy-3-methyl-4-propylsulfanyl-5H-furan-2-one, p-hydroxyphenethyl trans-ferulate, methyl 4-hydroxyl cinnamate and ferulic acid methyl ester. The last three compounds were confirmed as active QR-inducers.