2012 Annual Report
1a.Objectives (from AD-416):
The overall goal of this project is to discover, develop and foster commercialization of new bioactive products as new pharmaceuticals or agrichemicals, and to identify, characterize and develop plants for production of pharmaceuticals or pesticides as potential alternative crops.
1b.Approach (from AD-416):
(1) Development of strategies for rational collection of terrestrial, aquatic and marine plants, as well as microbes, as a source of novel bioactive natural products. (2) Discovery and development of novel pharmaceutically or agriculturally useful natural products from higher plants (3) Identification and investigation of new mechanistic targets that may be used in the discovery of pesticides and anti-infective and anti-cancer agents. (4) Development of methods and technologies to authenticate, pharmacologically characterize, and chemically analyze higher plants as sources of pharmaceuticals or botanical supplements. (5) Investigations of selections, cloning, propagation, agronomics, cultivation, harvesting and processing of medicinal plants in relation to the chemistry of desired pharmaceutically or agriculturally useful natural products.
Researchers at the National Center for Natural Products Research (NCNPR) at the University of Mississippi, Oxford, MS, maintained basic discovery operations, with emphasis on the discovery of antifungals, anticancer, anti-inflammatory agents and immunomodulating agents. Plant materials continue to be sourced for screening from NCNPR plant collections and from numerous collaborators, and 700 plant samples were added to the inventory this year. Over 4,000 natural product crude extracts, semi-purified fractions and purified compounds were screened for biological activities against specific molecular targets and whole cell systems. As part of continuing efforts in the search for anti-infective, anti-cancer, and immunomodulator/anti-inflammatory leads from natural sources, more than 130 compounds (including 13 new natural products) were identified from plants, marine sponges, and fungi. Many showed potent phytotoxic, antifungal, antibacterial, or antimalarial activities. Over 400 of NCNCPR isolated actives 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 NCNPR scientists have selected a number of these compounds for more advanced studies, 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., researchers at NCNPR have continued the development of lead compounds shown to be effective in animal models for desensitization to poison ivy dermatitis. Two leads in the poison ivy project are now undergoing formulation development, and bioavailability and toxicology studies. Construction of new facilities of the Medicinal Plant Garden at the University of Mississippi was completed this year, and work has begun to develop the outdoor growing sites. The completed facilities include a laboratory building, horticulture building, greenhouse, shade house, and equipment building. These facilities will enhance the capabilities of NCNPR to cultivate and process medicinal plants to be used in the discovery program. NCNPR continued a major construction planning project this year to complete its major research building with a 90,000 sq. ft. research wing. Construction documents were reviewed and approved by the funding agencies (Health Resources and Services Administration; National Institutes of Health) and a construction contract has been awarded for the project which will be completed in March, 2014. The new research wing will expand and enhance the research capabilities of NCNPR with a second plant specimen repository, herbarium, and laboratories for plant tissue cultures, cellular cultures, scale-up isolation and synthetic chemistry.