Location: Natural Products Utilization Research2020 Annual Report
The main objective of this project is to isolate and identify compounds from natural sources with pesticidal activity or have properties that are beneficial for human health. The overall goal is to be able to provide compound(s) amenable for commercial development as a pesticide or identify a “high value” plant with unique bioactive compounds. Over the next 5 years, we will focus on the following objectives: Objective 1: Enable, from a technological standpoint, new commercial biopesticides; and identify optimum production practices for the plants from which these biopesticides are derived. Subobjective 1.1: Identify nematicidal compounds from tall fescue. Subobjective 1.2. Discover natural product based fungicides from plant extract collections or other useful sources for US agriculture. Subobjective 1.3: Investigation of cashew nut shell liquid for insecticide activity and synthetic modification of the isolated compounds to gain insights into structure-activity relationship. Sub-objective 1.4: Discover natural product based herbicidal and insecticidal compounds from crude plants and plant endophyte extract collections. Objective 2: Identify human bioactive compounds in select plants and herbs, and determine plant growth conditions to enhance or optimize bioactive compound concentrations. Subobjective 2.1: Identify anti-adipocyte compound(s) in Scutellaria ocmulgee and determine the effect of various growth conditions on the bioactive compound(s).
An “activity-guided” isolation approach will be employed in efforts to discover novel bioactive compounds. Focus will be on isolating single compounds from active fractions. The che mical structure of bioactive compounds isolated will be elucidated using a combination of spectroscopic techniques such as ultraviolet, infrared, mass spectrometry and nuclear magnetic resonance spectroscopy. Simple structure modification of the bioactive constituent(s) and synthesis of analogs will be performed for activity optimization. In general, four projects are included in the plan, employing specific approaches. These include: 1) Identification of nematotoxic compound(s) from tall fescue cultivar Jesup (Max-Q). Isolation will be guided by an in vitro assay on inhibition of nematodes. The activity of the isolated nematotoxic compound will be tested in soil. 2) Identification of fungicidal compound(s) from select plants from China. Isolation will be guided using in vitro assays against Botrytis cinerea, Colletotrichum species, Fusarium species, and Phomopsis species. The activity of isolated compounds will be tested in detached leaf assays. 3) Identification of compound(s) from cashew nut shell liquid with insecticidal activity. Isolation will be performed using assays to determine activity against mosquito (Aedis egypti) larvae and adult. Analogs of the mosquito larvicidal/adulticdal compound(s) will be synthesized following standard synthetic procedures such as Friedel-Crafts acylation reaction. 4) Identification of anti-obesity compound from Scutellaria ocmulgee. Isolation of compounds will be performed using inhibition of adipocyte differentiation as acidity indicator. Anti-adipocyte compounds isolated will be used as chemical markers in associated study determining the appropriate agronomic practices to generate highest amount of anti-adipocyte compound(s) and biomass.
This is the final progress report for this project; replaced with bridging project #6060-41000-015-00D pending completion of National Program 306 research review. This project lost two scientists during the last two years of the project. It effectively was completed with one ARS researcher. Potent pytotoxins from toothpickweed identified. Plants constitute a rich source of novel and structurally diverse phytotoxic compounds to be explored in searching for effective and environmentally safe herbicides. Toothpickweed (Ammi visnaga) was subjected to phytotoxicity-guided fractionation. Two compounds, khellin and visnagin, whose herbicidal activity had not been described before were found to be highly phytotoxic. In laboratory assays, khellin and visnagin inhibited the growth of lettuce and duckweed. Also, both compounds reduced the growth of the weeds ryegrass, morningglory, foxtail and millet. The inhibitory activities of these compounds were similar to those of the commercial herbicides acetochlor and glyphosate in the lab bioassays. These results support the potential of visnagin, and possibly khellin, as bioherbicides or lead molecules for the development of new herbicides. Mode of action studies suggested that the compounds have a unique mode of action. Patents (WO 2017/115333 Al) have been filed related to the use of visnagin and khellin as bioherbicides. A new phytotoxic diterpene carbon skeleton from Eragrostis plana. Eragrostis plana is a problematic invasive plant with reported allelopathic potential. Isolated and identified phytotoxic compounds from leaves and roots of E. plana, a bioassay-directed isolation of the bioactive constituents was performed. This is the first report on a new diterpene carbon skeleton, the neocassanes. The most active of these compounds inhibited the growth of duckweed 50% at a concentration of 59 ± 15 µM which is better than some commercial herbicides in this assay. The description of the newly discovered compounds, besides contributing to the chemical characterization of the species, may be the first step in the study of the potential of these compounds as bioherbicides. A process for producing enriched capsinoids. Capsinoids (capsiate and derivitives) are non-pungent analogs of capsaicinoids that were first isolated from the sweet pepper cv. CH-19. Capsinoids offer similar types of biological activity as capsaicinoids. Capsiate can be chemically synthesized - though the process is lengthy, expensive, and the yield is low. A Capsicum annum mutant that produces high levels of capsiate was reported in 2014. We have developed a process and a patent has been awarded that involves a method for the extraction and purification of capsiate from this mutant and is applicable to the isolation of capsiate (capsinoids) from other Capsicum annuum cvs. and species. This capsiate enriched fraction is currently being evaluated for its ability to promote a drop in body temperature. This is the first step in understanding the role of our capsiate product in weight management. This work is being done by colleagues at McGovern Medical School. Pterostilbene, a bioactive component of blueberries and grapes, shows structural similarity to resveratrol, and exhibits antioxidant, anti-inflammatory, anti-cancer, hypoglycemic, and cholesterol lowering effects. Recent evidence indicates that pterostilbene is an agonist of the nuclear receptor, peroxisome proliferator-activated receptor-alpha (PPAR-a). Taken together, our studies demonstrate that pterostilbene, a natural compound and PPAR-a agonist, modulate several AMP-activated kinase (AMPK)-dependent metabolic functions. The results of the present study suggest that pterostilbene may have beneficial effects in the prevention and management of type 2 diabetes and related disorders. In this study, we found that pterostilbene activated AMPKe and increased the expression of fatty acid oxidation genes, including acyl CoA oxidase and carnitine palmitoyl transferase-1. Evaluating species for double utilization is a new approach to add value to lignocellulosic feedstock production. We evaluated selected essential oil crops peppermint (Mentha x piperita L.), ‘Scotch’ spearmint (M. x gracilis Sole), Japanese cornmint (M. canadensis L.), sweet sagewort (Artemisia annua L.), and compared them to switchgrass (Panicum virgatum L.) as lignocellulosic feedstock for ethanol production and for production of high-value natural products. Treatments affected the concentration of essential oil constituents, however, the oil composition remained within the normal range for the respective species. Estimated ethanol production from the alternative crops were similar to the one from switchgrass. Additional incomes from the essential oil sells would be $1,055 - 5,132 ha-1 from peppermint, $1,309 - 5,580 ha-1 from spearmint, $510 - 2,460 ha-1 from Japanese cornmint, and $3,613 ha-1 from sweet sagewort. The tested species could be used as supplemental crops for biofuel feedstock in irrigated areas. The advantage of the proposed crops over other lignocellulosic species is the production of high-value natural products, which may offset production costs, foster the development of new value-added products, and be more attractive to growers.
Ibrahim, M.A., Cantrell, C.L., Jeliazkova, E.A., Astatkie, T., Zheljazkov, V.D. 2020. Utilization of nutmeg (Myristica fragrans Houtt.) seed hydrodistillation time to produce essential oil fractions with varied compositions and pharmacological effects. Molecules. 25(3):565. https://doi.org/10.3390/molecules25030565.
Semerdjieva, I.B., Zheljazkov, V.D., Cantrell, C.L., Astatkie, T., Ali, A. 2020. Essential oil yield and composition of the Balkan endemic Satureja pilosa Velen. (Lamiaceae). Molecules. 25(4):827. https://doi.org/10.3390/molecules25040827.
Nocera, P., Bajsa Hirschel, J.N., Masi, M., Ross, S.A., Cantrell, C.L., Duke, S.O., Surico, G., Evidente, A. 2020. Secondary metabolites of Thymelaea hirsuta, a plant collected from the Sicilian Island of Lampedusa. Natural Product Research. https://doi.org/10.1080/14786419.2020.1752212.
Liu, X., Yu, W., Min, L., Wedge, D., Tan, C., Weng, J., Wu, H., Cantrell, C.L., Bajsa Hirschel, J.N., Hua, X., Duke, S.O. 2020. Synthesis and pesticidal activities of new Quinoxalines. Journal of Agricultural and Food Chemistry. 68:7324-7332. https://doi.org/10.1021/acs.jafc.0c01042.
Perera, W.H., Meepagala, K.M., Wedge, D.E., Duke, S.O. 2020. Sesquiterpenoids from culture of the fungus Stereum complicatum (Steraceae): Structural diversity, antifungal, and phytotoxic activities. Phytochemistry Letters. 37:51-58. https://doi.org/10.1016/j.phytol.2020.03.012.
Yu, W., Zhai, Z., Min, L., Wedge, D.E., Duke, S.O., Wu, H., Weng, J., Tan, C., Zhang, Y., Liu, X. 2019. Synthesis and biological activity of novel 1,3,4-oxadiazole derivatives containing a pyrazole moiety. Research on Chemical Intermediates. 45:5989-6001. https://doi.org/10.1007/s11164-019-04015-8.
Lazzara, N.C., Rosano, R.J., Vagadia, P.P., Giovine, M.T., Bezpalko, M.W., Piro, N.A., Kassel, W.S., Boyko, W.J., Zubris, D.L., Schrader, K.K., Wedge, D.E., Duke, S.O., and Giuliano, R.M. Synthesis and biological evaluation of 6-[(1R)-1-hydroxyethyl]-2,4a(R),6(S),8a(R)-tetrahydropyrano-[3,2-b]-pyran-2-one and structural analogues of the putative structure of Diplopyrone. The Journal of Organic Chemistry. 2019;84:666-678. https://doi.org/10.1021/acs.joc.8b02490.