2007 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 pharmaceuticals 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; (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; and, (3) Selection, agronomics and analysis of medicinally important plants and their derived products.
6408-21410-007-03S--SCA with University of MS--Maintained our basic discovery operations, with emphasis on the discovery of antifungals, anticancer, antiinflammatory agents and immunomodulating agents. Continued to source plant materials for screening from the Missouri Botanical Garden, New York Botanical Garden, Kenya Academy of Sciences, as well as our own plant collections and those of many collaborators and added 918 plant samples to our inventory this year. Over 6,600 natural product crude extracts, semi-purified fractions and purified compounds were screened in 2006-2007 for biological activities against specific molecular targets and/or whole cell systems. As efforts continue in the search for anti-infective, anti-cancer, and immunomodulator/anti-inflammatory leads from natural sources, Completed bioassay-guided chemical investigation on more than 30 species. As a result, more than 80 including 35 new natural products were identified from plants, marine sponges, and fungi. They showed potent phytotoxic, antifungal, antibacterial, and/or antimalarial activities. A patent application is to be filed for one of these classes of compounds as potential antifungal and antimalarial agents. More than 40 of our isolated actives have been characterized in more detailed follow-up assays, in order to determine their mode of action, pharmaceutical properties, toxicity, and selectivity across a range of assays. Additionally, we have selected a number of these compounds for more advanced study, whether for characterizing mechanisms of action, determining suitability for further pharmaceutical development, or evaluation in disease models in preclinical studies, or in field applications in the case of agrichemicals. These studies require considerable dedication of resources, first to obtain quantities of the natural product to be evaluated, and second in the costs/manpower required for conducting the studies. Identified 6 new antimalarial leads in the past year, and 8 new antifungal leads that have been scaled up and progressed to animal testing. One synthetic anti-cancer agent has been further tested in animals. Also tested in this past year the efficacy of several urushiol derivatives [the toxic principle of poison ivy] for desensitization to poison ivy dermatitis. These have been developed under an SBIR grant from the NIH, in collaboration with ElSohly Laboratories, Inc. Two of these hold great promise for developing desensitizing or protective agents. Our “Living Collection” of medicinal plants grew to over 900 species during the 06/07 FY. Our seedbank of medicinal plants now stands at 450 species. Demonstration plots of several medicinal herbs are grown each year in our Medicinal Plant Garden. Made authentic vouchers of 14 species of Salvia from our living collection. Evaluated Scutellaria laterifolia with regard to cultivability, yields, and harvesting techniques and Echinacea purpurea performance (4 clones) was evaluated for biomass production and bioactivity. Smallanthus sonchifolius (Yacon), a South American species, was evaluated in a preliminary study for biomass production under Mississippi climate conditions and persistability.
Major Accomplishments 2006-2007:
Antifungal natural products--The National Center for Natural Products Research (NCNPR) at the University of Mississippi has a long-standing antifungal natural product discovery program. This project has been supported by substantial NIH funding for the last 17 years, and many important achievements have resulted, with significant developments in this past year. This project spans from screening and isolation of antifungal compounds from nature through to studies of their mechanisms of action and their potential utility as fungicides and for pharmaceutical applications. Discoveries from previous years have been significantly advanced, and, by profiling gene responses to the compound, a new mode of action has been identified for one of the novel classes with potential fungicidal activity. This year a patent was issued [jointly owned by NCNPR and ARS/Natural Products Utilization Research Unit (NPURU)] for another novel class. These represent scientific advances in our understanding of naturally occurring antifungal compounds in plants, and in approaches to fungicide development, their mechanisms of action, and perhaps to pharmaceutical antifungal development.
This accomplishment addresses the ARS National Program Action Plan Problem Statement 2C of NP302: Developing High-Value Products. Identification of novel plant-derived natural products with potential pharmaceutical or agricultural uses
Antimalarial natural products--In the past year, the NCNPR was able to identify and secure external funding from the Medicines for Malaria Venture, a non-profit foundation based in Geneva, to support research on 6 natural product classes isolated and identified over the last few years. These plant-derived and fungal-derived compounds show potent antimalarial activity in the laboratory, and these will be explored for their utility as new drug leads for antimalarial drug development. Malaria kills more than 2 million people each year world-wide, most of them children. Though most malaria deaths occur in the developing world, because of the magnitude of the problem, the economic impact of the disease is felt in wealthier nations, including the United States, who spend billions of dollars each year to combat the disease. This work represents a potentially important technical advance in developing new antimalarial drugs from nature.
This accomplishment addresses the ARS National Program Action Plan Problem Statement 2C of NP302: Developing High-Value Products. Identification of novel plant-derived natural products with potential pharmaceutical or agricultural uses.
5.Significant Activities that Support Special Target Populations
|Number of new CRADAs and MTAs||30|
|Number of active CRADAs and MTAs||50|
|Number of invention disclosures submitted||6|
|Number of patent applications filed||4|
|Number of U.S. patents granted||4|
|Number of new commercial licenses granted||4|
|Number of web sites managed||2|
|Number of non-peer reviewed presentations and proceedings||3|
|Number of newspaper articles and other presentations for non-science audiences||4|