White Point Systems: About Natural Products

About Natural Products

Natural products are chemical or genetic materials derived from nature that are commonly used in the pharmaceutical drug discovery industry. Because chemical diversity in the natural environment is based on biological plus geographic diversity, researchers travel the world acquiring samples to evaluate in their drug discovery screens.

The natural environment is a rich source of structurally diverse chemical compounds that are used in drug discovery. Many drugs on the market today were discovered from natural sources; two important examples include the analgesic activity of aspirin from the bark of the willow tree, which is known from folklore, and the antibiotic activity of penicillin from molds of the genus Penicillium discovered serendipitously in the laboratory. Today, drug discovery is performed using two different methods: the “rational” and “empirical” approaches. Rational drug discovery is based upon the molecular origin of disease and the design of chemical compounds to act as antagonists that inhibit the disease process. Empirical drug discovery is based upon screening large numbers of chemical compounds for activity against therapeutic targets (=bioassays) felt to be of predictive use. Most of the drugs on the market today were discovered from natural sources using the empirical method.

The technology base to support “rational” drug discovery at industrial levels is at least a generation away, and current screening technologies using “empirical” methods have aligned the field of drug discovery to realistic proportions. The trend in drug discovery screening is towards mechanism-based assays that can be performed in a matter of minutes, in contrast to whole-cell based assays that require days. This trend is supported by laboratory robotics and information handling technologies which together define the emerging field of “high-throughput screening” -- drug discovery screens capable of testing upwards of 100,000 substances per week against several different disease targets. The trends in high-throughput screening are toward smaller test substance quantities and are consistent with sustainable harvest and conservation initiatives.

Drug discovery screens based on the “empirical” method require access to chemical diversity and frequently look to nature for a library of structurally diverse chemical compounds. Synthetic and combinatorial chemistry methods also provide an important source of chemical diversity for discovery screens, but provide only chemical analogs of a limited set of structural types. The recently FDA approved anticancer agent, Taxol, from the Pacific yew tree Taxus brevifolia, is an important example of “empirical” drug discovery using natural product chemicals; synthetic and combinatorial methods would not yield this complex structural type.

Natural products chemicals are extracted from the biomass of terrestrial plants, marine organisms, and microorganism fermentation broths. A crude extract from one source organism typically contains scores of novel, structurally diverse chemical types. Biological diversity plus geographic diversity give rise to natural products chemical diversity. Drug discovery efforts look to a wide variety of sources to achieve a high level of chemical diversity, and must document the sources of this diversity.

Natural products chemicals have played, and will continue to play, a key role in drug discovery. Screening natural products extracts, however, is expensive when compared with synthetic and combinatorial chemical libraries. Biological activity directed isolation studies and structural elucidation of unknown compounds add to the expense. Acquiring and tracking natural products source organism collections have extended requirements for information handling. Combining these requirements within one comprehensive system, NAPIS ^® will not only reduce costs, but can provide the leverage to convert assets for guiding future efforts.