The overall aim of this research """"""""Organoselenium Compounds from High Selenium Garlic"""""""", as one component of the Program Project, is to identify and synthesize novel organoselenium compounds that have good activity as inhibitors of mammary carcinogenesis and at the same time possess low toxicity.
The specific aim of this research is to fully identify selenium compounds from high-selenium garlic, as well as those selenium compounds present in unenriched garlic, to develop syntheses of these and related compounds and to provide synthetic samples to other members of the program project for in vitro and in vivo testing, to support program project members in analysis and identification of unknown organoselenium and mixed selenium-sulfur compounds resulting from project research, and to provide background mechanistic information on selenium metabolism in Allium spp. plants. In the longer term, based upon the initial results of biological testing, and following discussions with other project participants, additional syntheses will be designed and samples will be prepared and evaluated to optimize biological activity. Several different approaches will be used to identify the garlic selenoamino acids and to circumvent past difficulties in this area, due to the fact that the sulfur analogs of the selenoamino acids are present as the overwhelming components in these plants. Initial efforts will involve synthesis of a series of selenoamino acids, including isotopically labelled samples, characterization, development of chromatographic methods for separation from their sulfur counterparts, and determination of the headspace products formed when these selenoamino acids are mixed with garlic homogenates, using a variety of analytical techniques (GC-MS, HPLC, LC-MS/MS, SFC-MSD, CE). Nonpolar, volatile selenium-sulfur compounds related to compounds identified in garlic distilled oil will be prepared and evaluated for antitumor activity. The techniques of GC-AED (atomic emission detector) and LC-ICP (inductively coupled plasma) will be used for element specific analysis of complex mixtures containing selenium and other elements, including carbon- 13. Capillary electrophoresis (CE) will be used to achieve high resolution separation of selenium- and sulfur-containing amino acids. Supercritical fluid chromatography (SFC) will be explored as a means of separating relatively nonpolar, thermally unstable selenium compounds.
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