2013 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 MS, Oxford, MS, maintained basic discovery operations, with emphasis on the discovery of antifungals, anticancer, anti-inflammatory agents and immunomodulating agents. Scientists at NCNPR continued to source plant materials for screening from our own plant collections and from numerous collaborators. Over 1,400 plant samples were added to the NCNPR inventory this year. Over 14,000 natural product\crude extracts, semi-purified fractions and purified compounds were screended for biological activities against specific molecular targets and whole cell systems. As part of continuing efforts in the search for anti-infective, anticancer, and immunomodulator/anti-inflammatory leads from natural sources, more than 150 compounds (including 15 new natural products) were identified from plants, marine sponges, and fungi. Many of these showed potent phytotoxic, antifungal, antibacterial, or antimalarial activities. Over 150 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., development of a product shown to be effective in animal models for desensitization to poison ivy dermatitis continues. The lead compound in the poison ivy project is now undergoing advanced toxicology studies. With new facilities of the Medicinal Plant Garden at the University of Mississippi now complete, the outdoor growing sites are being developed and commissioned with plantings of various species. This new facility enhances the capabilities of NCNPR to cultivate and process medicinal plants to be used in the discovery program. NCNPR began construction of a 97,000 sq. ft. research wing this year and it is expected to be completed by 2015. 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.