Progress 07/01/05 to 06/30/08
Outputs
OUTPUTS: Contract pulping of hesperaloe fiber (shipped from Maricopa, Arizona in 2005) was completed. About 12 tones of bleached hesperaloe pulp were made. Completed lab pulping work showed that practicable cooking conditions, especially cooking liquor to fiber ratio, could be used to affect a higher-strength hesperaloe pulp. Additional lab bleaching work was made to simulate typical operating conditions. Papermaking trails are now being done at the pilot scale to demonstrate the unique properties of the hesperaloe pulp for the manufacture of ultra lightweight printing paper, including papermaking, coating, supercalendaring and printing. The natural products from desert plants work involved two major projects. In the first project two plants were evaluated (Valeriana sorbifolia and Valeriana officinalis, Valerian) for their biologically active constituents. Four new diene valepotriates and five known compounds were isolated from the aerial parts of Valeriana sorbifolia occurring in the Sonoran desert. Investigation of valerian (root powder of Valeriana officinalis) resulted in the isolation of five new valepotriate hydrines and three previously unknown natural products together with four known compounds. In the second project, Withania somnifera (Indian winter cherry) was grown aeroponically to produce large quantities of the anticancer active compound, withaferin A, for the preparation of its analogs for structure-activity relationship studies. Other crops evaluated for natural product use in the southwestern U.S. include sweet sorghum. This crop can grow on marginal lands and requires less water than other bioenergy sources and since the juice is in the stems, after pressing, it can be directly fermented into ethanol. Our objective was to begin screening the available germplasm for potential production in the arid and semiarid regions of the U.S. In 2006, 31 lines were planted and 25 lines in 2007, with six being common to both years. Plants were measured for height, insect damage, and lodging. We found the major components of ethanol yield are biomass, percentage of juice, percentage of stalk, and the percentage of carbohydrates in the juice. PARTICIPANTS: Nothing significant to report during this reporting period. TARGET AUDIENCES: Nothing significant to report during this reporting period. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.
Impacts
Ultra lightweight supercalendared paper was produced using a blend of 15% heseperaloe pulp and 85% deinked old newspaper pulp. The desired ultra lightweight base paper was made; supercalendaring was completed off-machine. Some samples of ultra lightweight hesperaloe pulp-based printing paper are available to prospective commercial customers. The significance of the natural products from desert plants part of the project is two-fold. First, both Valeriana species investigated contained new natural products and all compounds encountered were shown to have weak to moderate cytotoxicity against the human metastatic prostate cancer cell line, PC-3M. Second, the soil-less aeroponic technique was shown to be a rapid and convenient method for the large-scale production of the anticancer active natural product, withaferin A. In the screening of the sweet sorghum germplasm as a potential bioenergy crop for the southwestern deserts, one sweet sorghum line, containing combination of good potential production characteristics was selected for potential commercial production.
Publications
- 2,3-Dihydrowithaferin A-3 beta-O-sulfate, A New Potential Prodrug of Withaferin A from Aeroponically-Grown Withania somnifera, Xu, Y.; Marron, M. T.; Seddon, E.; Ray, D. T.; Whitesell, L.; Gunatilaka, A.A.L. Bioorganic & Medicinal Chemistry, 2008, submitted.
- Sorbifolivaltrates A-D, Diene Valepotriates from Valeriana sorbifolia, Xu, Y.; McLaughlin, S. P.; Gunatilaka, A. A. L. Journal of Natural Products. 2007, 70, 2045-2048.
|
Progress 07/01/06 to 06/30/07
Outputs
The Hesperaloe pulp was produced by one of our industry partners during this grant period and will be used in a papermaking trial. The paper mill will produce 42.5g/m2 printing paper containing 15% Hesperaloe pulp and 85% de-inked old newspaper pulp. This paper will then be used in a follow-on printing trial. Hesperaloe fields were maintained and monitored for use in pulping and paper making trials. Measurements (total biomass) of the harvested acres and estimates of total biomass were made. Hesperaloe leaf harvesting requires that leaves be stored and shipped to a distant pulping plant, thus the leaves must be cut, crushed, dried, and baled for storage and shipping. Crushing the leaves allows them to dry and bleach in the sun so they can be baled and stored without deteriorating. Baling provides a means of packaging the dried leaves so they can be economically transported to the pulping plant. One concern in the harvesting, drying, and baling of the material is the
foreign matter found in the bales at the pulping facility. The crushed material is spread on the field, but being wet soil particles adhere to the crushed leaves. After drying the leaves are placed in the trailer with pitchforks, and inevitably more non-leaf material is incorporated with the dry crushed leaves. The leaves are transported to an open field for further drying and raking into windrows. As these windrows are formed, more dirt particles can be incorporated in the harvested leaves. Lastly, during baling, the metal fingers which lift the dry material into the machine can pick up additional material during this process. A solution to this problem will probably involve washing the leaf material in a moving bath at the processing plant. We continue to work on natural product-based drug discovery by biological screening, bioassay-directed fractionation, structure elucidation and production of biologically active natural products. With funding from this grant over 500 plants have
been collected from the southwest U.S., taxonomically authenticated, and herbarium specimens have been deposited at the University of Arizona Herbarium. The dried and powdered plant material have been sequentially extracted with dichloromethane/methanol (1:1/v:v), methanol, and water generating over 1500 extracts, which are currently stored in the library of plant extracts at the Natural Products Center. Several extracts from this library have been evaluated for their potential anti-cancer activity, and extracts active in cancer cell cytotoxicity assays were subjected to bioassay-guided fractionations to isolate and characterize compounds responsible for their potential anti-cancer activity. Investigation of Zinnia grandiflora has led to the identification of three new cytotoxic sesquiterpene lactones, and Valeriana sorbifolia has provided nine cytotoxic valepotriates of which four were found to be new natural products. Several representative samples from our library of extracts were
submitted for anti-inflammatory activity testing. The results obtained suggested that crude extracts had to be processed before subjecting them to the COX assays.
Impacts
Efforts to domesticate Hesperaloe funifera as a feedstock for fiber production are motivated by the need to diversify agriculture and provide alternatives to subsided surplus-production of commodity crops. Progress has been made in the development of paper products, and the University of Arizona continues its collaborations with the pulp, paper and printing industries. In order to survive harsh conditions, arid and semi-arid plants have to possess various morphological and physiological adaptations. Some of the physiological adaptations of these organisms may lead to the production of unique natural products with potential agricultural and medicinal uses. Investigation of these plants for useful natural products could therefore lead to: (1) the discovery of new arid land cash crops producing novel higher-priced specialty products; and (2) generation of new industries for the production of natural products for use in the agrochemical and pharmaceutical industries
helping the ailing rural economies of many arid areas in the southwestern United States. This project will generate a more ecologically sound use of arid lands and will result in added jobs and industries for the agricultural sectors of the southwestern United States.
Publications
- Vieira, H.S., J. Takahashi, A.A.L. Gunatilaka, and M.A. Boaventura. 2006. 1H and 13C NMR Signal Assignments of a Novel Baeyer-Villiger Originated Diterpene Lactone. Magnetic Resonance in Chemistry 44(2):146-150.
- Gunatilaka, A.A.L. 2006. Natural Products from Plant-Associated Microorganisms: Distribution, Structural Diversity, Bioactivity, and Implications of Their Occurrence. Journal of Natural Products 69(3):509-526.
- Wijeratne, E.M.K., T.J. Turbyville, A. Fritz, L. Whitesell, and A.A.L. Gunatilaka. 2006. A New Dihydroxanthenone from a Plant-Associated Strain of the Fungus Chaetomium globosum Demonstrates Anticancer Activity. Bioorganic Medicinal Chemistry 14(23):7917-7923.
- Wijeratne, E.M.K., M.X. Liu, B. Kantipudi, C.B. Brochini, A.A.L. Gunatilaka, and L.M. Canfield. 2006. Synthesis and Preliminary Biological Evaluation of β-Carotene and Retinoic Acid Oxidation Products. Bioorganic Medicinal Chemistry 14(23):7875-7879.
- Zhan, J., and A.A.L. Gunatilaka. 2006. Microbial Transformation of Amino- and Hydroxyanthraquinones by Beauveria bassiana ATCC 7159. Journal of Naural. Products 69(10): 1525-1527.
- Wijeratne, E.M.K., P.A. Paranagama, and A.A.L. Gunatilaka. 2006. Five New Isocoumarins from Sonoran Desert Plant-Associated Fungal Strains Paraphaeosphaeria quadriseptata and Chaetomium chiversii. Tetrahedron 62(36):8439-8446.
- Subramanian, B., A. Nakeff, K. Tenney, P. Crews, A.A.L. Gunatilaka, and F. Valeriote. 2006. A New Paradigm for the Development of Anticancer Agents from Natural Products. Journal of Experimental Therapeutics and Oncology 5(3):195-204.
- Zhan, J. and A.A.L. Gunatilaka. 2006. Selective 4-0-Methylglycosylation of the Pentahydroxy-flavanoid Quercetin by Baeuveria bassian. Biocatalytic Biotransformation 24:396-399.
- Zhan, J., G.M.K.B. Gunaherath, E.M.K. Wijeratne, and A.A.L. Gunatilaka. 2007. Asperpyrone D and Other Metabolites of the Plant-Associated Fungal Strain Aspergillus tubingensis. Phytochemistry 68:368-372.
- Zhan, J., A.M. Burns, M.X. Liu, S.H. Faith and A.A.L. Gunatilaka. 2007. Search for Cell Motility and Angiogenesis Inhibitors with Potential Anticancer Activity: Beauvericin and Other Constituents of Two Endophytic Strains of Fusarium oxysporum. Journal of Natural Products 70(2):227-232.
- Falsey, R., M.T. Marron, G.M.K. Gunaherath, N. Shirahatti, D. Mahadevan, A.A.L. Gunatilaka, and L. Whitesell. 2006. Actin Microfilament Aggregation Induced by Withaferin A is Mediated by Annexin II. Nature Chemical Biology 2(1):33-38.
- Turbyville, T.T., E.M.K. Wijeratne, M.X. Liu, A.M. Burns, C.J. Seliga, L. Luevano, C.L. David, S.H. Faeth, L. Whitesell, and A.A.L. Gunatilaka. 2006. Search for Hsp90 Inhibitors with Potential Anticancer Activity: Isolation and SAR Studies of Radicicol and Monocillin I from Two Plant-Associated Fungi of the Sonoran Desert. Journal of Natural Products 69(2):178-184.
|
Progress 07/01/05 to 06/30/06
Outputs
This project involves work with the novel paper-making-fiber plant, Hesperaloe funifera, and work with other desert plants producing natural products with potential commercial value. Hesperaloe has exceptionally high water-use efficiency and high productivity in arid climates; its fibers can be used in paper making and have strength properties superior to all currently used plant fibers, including those from virgin softwoods. Efforts in 2005 and 2006 were concentrated on pilot scale pulping and paper making in private-sector facilities, and continued development of harvesting and processing equipment at the University of Arizona Maricopa Agricultural Center. Commercial hydroxide pulping trials at the Ahlstrom Chirnside Mill in the UK were successful in producing a high strength pulp, but this mill was ultimately not successful in producing a pulp free of shives, unprocessed fragments of the leaf. Shive removal has been a major technical barrier. A pulping trial was
conducted at another mill in Olsany, Czech Republic. This latter mill used a soda pulping process which did dissolve the shives, but the pulp showed unexpected and unacceptable low strength. Tests made at the CSPP lab in Quebec showed that high concentration of pulping chemicals was responsible for the low strength. CSPP is currently evaluating the bleaching requirements for the soda pulp, which has a much lower brightness that the hydroxide pulp. Several rolls of paper composed of 15% hesperaloe and 85% deinked recycled newsprint were successfully made at the CSPP laboratory. Target basis weights of 40 to 45 grams per square meter were achieved. This may ultimately prove to be the highest value for hesperaloe fiber: as a strengthening agent for recycled newsprint. Limited progress has been made in lowering the costs of harvesting and drying hesperaloe leaves. Other objectives of the project focused on discovery and characterization of desert plants producing compounds with
anti-cancer and anti-inflammatory activity. Several plant species with high activity in the targeted anti-cancer bioassay were identified and bulk recollections were obtained. A sample of plants for the anti-inflammatory work was obtained, including several species used by Native Americans to treat inflammation-related ailments; these have all been extracted with three solvent systems: water, MEOH, and DCM. We have not successfully worked out procedures for the COX-1 and COX-2 bioassays and it may prove more cost-effective to subcontract this phase of the work. Several plant extracts active in biological assays for inhibition of cancer cell migration and proliferation/survival were subjected to bioactivity-guided fractionation and a variety of small molecule natural products with potential anticancer activity have been isolated and characterized. Winter cherry (Withania somnifera), grown aeroponically from seeds of Indian origin was found to contain the anticancer active compound
withaferin-A as the major metabolite suggesting that this process can be used to obtain a reasonable quantity of this compound for further biological evaluation.
Impacts
Because of its high water-use efficiency, Hesperaloe has the potential to become a low-water use crop for Arizona and other arid regions, pending successful resolution of the pulping and harvesting problems. Practical considerations will favor pulping on site to reduce harvest costs, integrating the production and processing of the crop in rural regions. This would result in both local environmental and economic benefits. With the recent removal of several anti-inflammatory drugs from the market, the work on desert plants with anti-inflammatory activity has the potential to identify new leads for safer compounds with COX-2 specific activity. It is increasingly recognized that biochemical pathways in the development of cancer and the inflammation response are related.
Publications
- No publications reported this period
|
|