2009 Annual Report
1a.Objectives (from AD-416)
Identify stress factors and modify biochemical feed stocks that can influence the production of legume phytochemicals. Test individual combinations of phytochemicals in human model systems. Characterize procedures that can enhance the levels of natural products having estrogenic, anticancer, or potential cancer preventative activities.
1b.Approach (from AD-416)
Soybean cultivars will initially be grown under well-controlled test tube conditions. After various growth periods, roots will be harvested and their natural products extracted. Selected compounds will be purified and identified using HPLC and various instrumental methods applicable to organic structural characterization such as MS, NMR, IR, and UV. These experiments will then be repeated in the presence of various stress factors such as cyst root nematodes, and in the presence of modified biochemical feed stocks such as aryl-substituted phenylalanine and cinnamic acid derivatives, in order to determine useful elicitation methods and to produce altered phytochemical materials, respectively. Interesting components will again be purified and identified, after which the pharmacologic properties for all materials will be assessed as either individual or combinations of phytochemicals using in vitro models for estrogenic, anticancer, and potential cancer preventative activities. The most promising natural products will be produced in larger quantities by scaling-up the appropriate controlled-growth conditions and by conducting chemical synthesis, as necessary, to support further pharmacological assessments in an expeditious manner. The latter will involve the use of in vivo models indicative of potential estrogenic activity, anticancer therapy, or cancer prevention in humans. Useful growing conditions connected to the most pharmacologically promising compounds or mixtures of components, will be extended to greenhouse settings and eventually to field environments.
In collaboration, we have shown that the soybean plant compounds called the glyceollins inhibit the growth of breast and ovarian cancer in vivo (in laboratory test animals). In order to further study the glyceollins activity in animal models, we have successfully developed a chemical synthetic scheme to produce two types of glyceollins, I and II. A synthetic route is desirable since the glyceollins (a mixture of glyceollin I, II, and III) have been difficult to purify from soy material as individual components. The overall synthesis route has been shown to have a yield of nearly 4% (percent conversion from starting materials), while also avoiding the wasteful use of solvents that was regarded as being undesirable in earlier synthetic routes. A large scale synthesis of 2g glyceollin I beginning from nearly 250 grams of starting material has been completed. Fortuitously, our novel synthetic step may also be useful for the production of related natural products that have already been advanced into clinical studies by other investigators. Taking advantage of this finding, we are now including these types of utilities in our chemical patent applications for the procedure to synthesize the glyceollins. At this point, we have firmly established a solid patent base around the intellectual property (IP) associated with the specific chemical production of the glyceollins, as well as providing further coverage for the various therapeutic applications that we have previously identified. Also, our research group is analyzing the effect of root cyst nematodes on soybean plants and have detected glyceollins in root tissues. The major impact of this research could lead to alternative or value-added uses of induced phytoestrogen (plant-derived estrogenic compounds) containing food and health products. Progress by cooperators was monitored through routine teleconferencing, meetings, and scientific presentations of information relating to the project at professional society meetings and conferences.