Natural derived or originated compounds still play a major role as drugs, and as lead structures for the development of synthetic molecules. About 50% of the drugs introduced to the market during the last 20 years are derived directly or indirectly from small biogenic molecules. In the future, natural products will continue to play a major role as active substances, model molecules for the discovery and validation of drug targets. A multidisciplinary approach to drug discovery involving the generation of truly novel molecular diversity from natural product sources, combined with total and combinatorial synthetic methodologies provides the best solution to increase the productivity in drug discovery and development. Screening for new drugs in plants implies the screening of extracts for the presence of novel compounds and an investigation of their biological activities. It is currently estimated that approximately 420,000 plant species exist in nature. For the purpose of lead discovery, or for the scientific validation of a traditional medicinal plant or a phytopharmaceutical, active principals in complex matrices need to be identified. Therefore, the interfacing of biological and chemical assessment becomes the critical issue. Drug discovery from plants can be guided by epidemiologic studies facilitated with computer assisted HPLC microfractionation and microplate technology. Epidemiologic studies have shown that high dietary flavonoid intake may be associated with decreased risk for cardiovascular disease. Chlamydia pneumoniae is a common human pathogen and epidemiological and clinical studies have shown a connection between chronic C. pneumoniae infection, atherosclerosis and the risk of myocardial infarction. We will present here the detection of natural compounds active against C. pneumoniae as an example.

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A previously isolated cDNA molecule from Gerbera hybrida (Asteraceae) codes for a new chalcone synthase-like polyketide synthase, 2-pyrone synthase (2PS). 2PS is able to synthesise 4-hydroxy-6-methyl-2-pyrone (triacetolactone), a putative precursor for gerberin and parasorboside, two abundant glucosides in gerbera. In this study, we show that gerbera plants transformed with the gene for 2PS in an antisense orientation and unable to synthesise gerberin and parasorboside are susceptible to Botrytis cinerea infection. In addition to the preformed glucosides, the transgenic plants also lack several compounds that are induced in control plants when infected with the mould. Some of these induced substances are effective in inhibiting fungal growth both in vitro and in vivo. Two of the phytoalexins were identified as the aglycones of gerberin and trans-parasorboside. The third phytoalexin is a rare coumarin, 4-hydroxy-5-methylcoumarin; however, it is typical of many plants of the sunflower family Asteraceae. The coumarin cannot be structurally derived from either gerberin or parasorboside, but may be derived from a related polyketide intermediate.

A reversed-phase HPLC method was developed using a computer simulation program for the identification of dried roots of Echinacea purpurea, E. angustifolia, E. pallida and Parthenium integrifolium. Hydrophilic and lipophilic compounds were analysed simultaneously leading to a two-fold decrease in analysis time compared to traditional HPLC methods.

High performance liquid chromatography (HPLC) micro-fractionation was successfully coupled to an automated 45Ca2+ uptake assay using GH4C1 cells for the separation of natural product extracts and for the primary detection of their calcium antagonistic components. The reliability of the procedure was first established with a reference solution consisting of pure compounds with a known effect on the Ca2+ uptake. No loss of activity was observed to occur after HPLC micro-fractionation. Extracts of Peucedanum palustre and Pinus sylvestris, showing high and no inhibition of Ca2+ uptake as total extracts, respectively, were analysed and the inhibitory activity of the P. palustre extract could be traced to two components, identified as columbianadin and isoimperatorin. As expected, no significant inhibition was observed with the micro-fractionated P. sylvestris samples. In summary, the procedure was found to be applicable for primary detection of calcium antagonistic components in complex matrices and to significantly reduce the time previously needed for bioactivity-guided isolation.