Screening natural product

Devlin, J.P., Carter, C., and Homon, C.A., High capacity screening natural products as immune regulators, in Economic and Medicinal Plant Research, Wagner, H. and Farnsworth, N.R., Eds., Academic Press, San Diego, 1991, chap. 4. 

For TM to be accepted into mainstream medical treatment, a likely scenario is the application of scientific methodologies and controls for TM development, evaluation, and production. Many of the tools for high throughput screening (HTS) and assay systems can be used to test the efficacy of TM, similar to the irrational approach of screening natural products. Pharmacology studies have to be conducted in accordance with Good Laboratory Practice (GLP). 

Perhaps the most exciting story about an anticancer agent derived from a natural product is that of Taxol . That story begins in 1958, when the National Cancer Institute began a program to screen natural products for substances that might have anticancer activity. The... 

Most inhibitors in this latter class were initially discovered by screening natural-products libraries or by structurebased de novo design. The most interesting examples of the nonpeptidic inhibitors from this group are the independently discovered but structurally... 

Cell-based assays have been important tools for finding drug candidates from the days of screening natural product extracts for antibacterial activity.57 With the development of molecular biology and advances in cell culture, many more ways to monitor specific biological processes in cultured cells have become possible. 

Poulsen S-A, Davis RA, Keys TG (2006) Screening natural product-based combinatorial library using FTICR mass spectrometry. Bioorg Med Chem 14 510-515... 

Drugs have been discovered by two, fundamentally opposite, approaches (Figure 35.1). The first approach identifies a substance that has a desirable physiological consequence when administered to a human being, to an appropriate animal, or to cells. Such substances can be discovered by serendipity, by the fractionation of plants or other materials known to have medicinal properties, or by screening natural products or other libraries of compounds. In this approach, a biological effect is known before the molecular target is identified. The mode of action of the substance is only later... 

Some pharmaceutical companies employ entire departments of B.S., M.S., and Ph.D. organic chemists to screen natural products for novel, pharmacologically active compounds. These natural products may originate in plants, fermentation broths, or animal matter. Scientists make the extractions and prepare the extracts for screening. Working in these departments, they also isolate, purify, characterize, and identify the compounds responsible for the activity. Biological assays direct the work, so that inactive substances squander no efforts or resources. 

The cephalostatins and ritterazines highlight the power of screening natural product extracts over currently fashionable synthetic combinatorial libraries in terms of structural novelty and complexity. Today, libraries are constructed by short sequences of synthetic transformations, whereas many natural products are the result of much longer and more creative pathways. 

ISHiTSUKA et aL screened natural products for antirhinoviral activity and reported that a flavone (Ro 09-0179), a potent antipicomavirus agent, was isolated from a Chinese medicinal herb (Agastache rugosa Kuntze) (173). We studied the antiviral effects on rhinovirus type 2 and found that morusin hydroperoxide (49), oxydihydromorusin (34), chalcomoracin (103), and compound A (31) had marginal anti-rhino viral activities (MIC, 1.25-2.5 ig/ml) (48). 

As sampling of chemical space will be even more sparse with increasing size of the molecules, it may be required to revert to other technologies like fragment-based screen, natural products, DNA-encoded libraries, or dynamic combinatorial chemistry to generate starting points for lead identification. 

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