The indole-derived compounds in cruciferous vegetables
Investigation of the Biological Role of Indole Derivatives in Cruciferous Vegetables and Synthesis of the Most Important Natural Compounds, their Analogs and Derivatives with the Aim to Obtain New Anticarcinogenic, Antitumor or Immunomodulating Compounds
Tech Area / Field
- CHE-ANL/Analytical Chemistry/Chemistry
- CHE-SYN/Basic and Synthetic Chemistry/Chemistry
- MED-DRG/Drug Discovery/Medicine
8 Project completed
Senior Project Manager
Zalouzhny A A
State Research Institute of Organic Chemistry and Technology, Russia, Moscow
- Gause Institute of New Antibiotics, Russia, Moscow
- University of California, USA, CA, Berkeley\nXechem International Inc., USA, NJ, New Brunswick\nKarolinska Institute, Sweden, Stockholm
Project summaryNumerous epidemiological studies and results from animal experiments suggest that high consumption of Brassica vegetables reduces the risk of developing cancer of various organs. Brassica vegetables, which belong to the family Cruciferae comprise all kinds of cabbages, Brussels sprout, broccoli, cauliflower, kohlrabi, turnip and swede. These vegetables contain compounds, which induce enzymes, which deactivate carcinogens and change metabolism of some endogenic compounds, e.g. estrogens. The indole compounds in these vegetables were identified as transformation products of the alkaloid glucobrassicin or related compounds, which degrade when plant cells are destroyed. These compounds undergo further transformations in an organism.
Till recent times investigators considered indole-3-carbinol (I3C) as the most important product of glucobrassicin degradation. However in the presence of L-ascorbic acid, which molar concentration in Brassica vegetables extracts is higher, than the concentration of glucobrassicins, the predominant product of glucobrassicin transformation is the product of L-ascorbic acid 2-C-alkylation called ascorbigen and in some vegetables - 1-methoxyascorbigen (neoascorbigen). These compounds undergo transformations in physiological conditions in acidic and slightly alkaline media. Preliminary experiments have demonstrated that the major indole compound which is present in blood of animals fed with ascorbigen is 1-deoxy-1-(indole-3-yl)-L-sorbopyranose. Biological role of this compound and other products of ascorbigen or neoascorbigen degradation remains to be clarified.
Earlier it was shown that synthetic 1-methylascorbigen is a highly active immunomodulator which protects animals from bacterial (gram-positive and gram-negative) or viral infections (including arbo-viruses). Search for new immunomodulators among compounds of this type is perspective.
Differently from existing projects, which attention is directed to indole-3-carbinol, in the presented program the research will be directed to the study of the biological properties of ascorbigen, neoascorbigen, and also synthesis and investigation of analogs of these compounds as potential antitumor, anticarcinogenic or immunomodulating substances.
The propose of the Project will consist of four stages, each of them being of scientific and practical significance.
First Stage will include studying biotransformation of ascorbigen and neoascorbigen, identification of the compounds formed and also clarifying role of ascorbigen and neoascorbigen as depot-forms of L-ascorbic acid.
Second Stage will include synthesis of most important natural compounds, their metabolites and analogs as potential cytostatic, antitumor or anticarcinogenic drugs or nutrient additives.
Third Stage will be understanding biological activities of the products of ascorbigen and neoascorbigen biotransformation.
Fourth Stage will include creation of an user database of new biological active compounds.
As an anticipated result of this Project, potential anticarcinogenic, antitumor or immunomodulating drugs of new type will be developed.
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