Bioassay development in natural product drug discovery

Bioactivity screening is an integral part of the natural product drug discovery process [1]. The bioactive compounds in the natural product extracts are screened utilizing e.g. whole cells, cell fractions, recombinant enzymes or biochemicals as targets. The screening of natural products provides a complementary structural diversity to synthetic chemistry and offers new low molecular weight lead compounds. Our work involves generating and screening of extract/compound libraries of biogenic origin for pharmaceutical purposes.

We have used microfractionation of plant and microbial extracts on HPLC combined with design and development of new bioactivity screening assays as an approach to find bioactive principals. Using HPLC microfractionation, components of crude extracts can be divided into fractions collected into microwell plates and subsequently subjected to diverse bioassays. Miniaturized screening assays have been developed with special emphasis on quality of the bioassays for e.g. susceptibility testing of Chlamydia pneumoniae utilizing time-resolved fluorometric immunoassay [2, 3]. The coupling of automated bioassay to analytical HPLC microfractionation greatly facilitated the classical process leading from a plant to pharmacologically active compound [4].

References: 1. Vuorela, P., Leinonen, M., Saikku, P., Tammela, P., Rauha, J.-P., Wennberg, T., Vuorela, H. (2004), Curr. Med. Chem. 11: 1375–1389. 2. Tammela, P. et al. (2004), Anal. Biochem. 333: 39–48. 3. Alvesalo, J. et al. (2006), J. Med. Chem. 49: 2353–2356. 4. Tammela, P. et al. (2004), Anal. Bioanal. Chem. 380: 614–618.