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United States Department of Agriculture

Agricultural Research Service

Research Project: DISCOVERY AND DEVELOPMENT OF NATURAL PRODUCT FOR PHARMACEUTICAL AND AGRICHEMICAL APPLICATIONS
2013 Annual Report


1a.Objectives (from AD-416):
The overall goal of this project is to discover, develop and foster commercialization of new bioactive natural products as new pharamceuticals or agrichemicals and to identify, characterize and develop medicinal plants for production of pharmaceuticals as potential alternative crops.


1b.Approach (from AD-416):
The approach includes a program of: (1) Discovery of secondary metabolites from natural resources with anti-infective and anti-cancer activities based on molecular and cell-based assays [NP301, C4, PS 4B]; (2) Characterizing mechanisms of action, selectivity, toxicity and functional activity for the best candidate compounds with anti-microbial and anti-cancer properties in secondary assays and in animal models [NP301, C4, PS 4B]; and (3)Selection, agronomics and analysis of medicinally important plants and their derived products [NP301, C4, PS 4B].


3.Progress Report:
This is a final report for this project. Researchers at the National Center for Natural Products Research (NCNPR) at the University of MS, Oxford, MS, maintained basic discovery operations, with emphasis on the discovery of antifungals, anticancer, anti-inflammatory agents and immunomodulating agents. Plant materials from the NPURU plant collections, as well as from numerous collaborators continue to be sourced for screening. NPURU continues to add plant samples to the inventory and screen natural product crude extracts, semi-purified fractions and purified compounds for biological activities against specific molecular targets and whole cell systems. As part of the continuing effort in the search for anti-infective, anticancer, and immunomodulator/anti-inflammatory leads from natural sources, many new natural products were identified from plants, marine sponges, and fungi. Many of these showed potent phytotoxic, antifungal, antibacterial, or antimalarial activities. A number of the isolated actives or extracts have been characterized in more detailed follow-up assays to determine their mode of action, pharmaceutical properties, toxicity, and selectivity across a range of assays. In addition to these basic operations, a number of these compounds have been selected for more advanced study, whether for characterizing mechanisms of action, determining suitability for further pharmaceutical development, evaluation in disease models in preclinical studies, or in field applications. In collaboration with ElSohly Laboratories, Inc., continued development of lead compounds are shown to be effective for treatment of poison ivy dermatitis. New facilities in progress include a new medicinal plant garden and a new research wing.


4.Accomplishments
1. Develop antifungal natural products. Because many organisms contain inherent protective mechanisms the natural environment is a rich source for compounds to treat fungal diseases. Scientists at the National Center for Natural Products Research (NCNPR) at the University of Mississippi aim to discover novel antifungal compounds for treating life-threatening opportunistic fungal infections. This ongoing program covers various aspects of drug discovery including screening and isolation of natural product antifungal compounds, determining their mechanism of action, and understanding potential resistance mechanisms. A number of promising agents were identified by screening natural product samples for antifungal activity against different fungal pathogens. Important achievements include the isolation and identification of new antifungal compounds, and the identification of new molecular pathways. These accomplishments may lead to new treatments for numerous diseases of plants, animals, and humans.

2. Develop agents for prevention/treatment of poison ivy dermatitis. Poison ivy is a widespread plant that causes an itching rash in most people who touch it. Scientists at the National Center for Natural Products Research (NCNPR) at the University of Mississippi are developing preventive treatments for poison ivy dermatitis. Two lead compounds shown to be effective in animal models for desensitization to poison ivy dermatitis are being advanced toward upcoming clinical studies. These accomplishments may lead to new products for a common but serious condition.

3. Develop treatments for cancer. A cancer research program requires a drug discovery program in order to explore all avenues of treatment. Scientists at the National Center for Natural Products Research (NCNPR) at the University of Mississippi operate the Drug Discovery Core of the University of Mississippi Medical Center (UMMC) Cancer Institute. A number of plant extracts and pure compounds were screened for anticancer activity. The most promising anticancer compounds will be produced in quantities required for further development and evaluation by the UMMC Cancer Institute, which may lead to new treatments for cancer.

4. Discovery of new drugs to prevent or treat diseases caused by protozoans. New drugs for malaria and leishmaniasis will reduce risk of treatment failure, reduce risk of developing resistance, and reduce side-effects of the drug now commonly used. Scientists at the National Center for Natural Products Research (NCNPR) at the University of Mississippi have discovered a number of novel anti-protozoal compounds. These accomplishments contribute to efforts to fight these widespread diseases.


Review Publications
Bharathi, A., Tekwani, B.L., Chauarasiya, N.D., Nanayakkara, D.N., Wang, Y., Khan, S.I., Adelli, V.R., Sahu, R.K., Elsohly, M.A., Mcchesney, J.D., Khan, I., Walker, L.A. 2013. Profiling primaquine metabolites in primary human hepatocytes by UPLC-QTOF-MS with 13c stable isotope labeling. Journal of Mass Spectrometry. 48(2):276-285.

Galal, A.M., Raman, V., Avula, B., Wang, Y., Rumalla, C.S., Weerasooriya, A.D., Khan, I.A. 2012. Comparative study of three Plumbago L. species (Plumbaginaceae) by microscopy, UPLC–UV and HPTLC analyses. Journal of Natural Medicine. 67:554-661.

Muhammad, I., Ibrahim, M.A., Khan, S.I., Jacob, M.R., Tekwani, B.L., Walker, L.A., Sameylenko, V. 2012. Pentacyclic ingamine-type alkaloids, a new antiplasmodial pharmacophore from the marine sponge petrosid Ng5 Sp5. Planta Medica. 78(15):1690-1697.

Avula, B., Wang, Y., Wang, M., Smillie, T.L., Khan, I.A. 2012. Simultaneous determination of sesquiterpenes and pyrrolizidine alkaloids from the rhizomes of petasites hybridus (L.) G.M. et Sch. and dietary supplements using UPLC-UV and LC-TOF methods. Journal of Pharmaceutical and Biomedical Analysis. 70:53-63.

Avula, B., Wang, Y., Wang, M., Shen, Y., Khan, I.A. 2013. Simultaneous determination and characterization of tannins and triterpene saponins from the fruits of various species of terminalia and phyllantus emblica using UPLC-UV-MS method: application to triphala. Planta Medica. 79(20:181-188.

Last Modified: 11/23/2014
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