Analyzing outcomes from a library-based screening against diverse targets

To what extent plant selection based on ethnomedical information contributes to the outcomes of library-based natural product lead discovery programs is a matter of debate. Therefore, we have performed a retrospective analysis of the outcomes from screening campaigns and follow-up discovery of active compounds with our in-house extract library. Using functional as well as mechanism-based assays, we screened for GABA_A receptor modulators, antiprotozoal activity against Plasmodium falciparum, Trypanosoma brucei rhodesiense and Leishmania donovani, anti-retroviral activity, and inhibition of DYRK1A, and we compared an ethnomedicine-based subset of the library with a subset of “randomly” collected plants. Very few samples gave hits in more than one assay. In the subset of traditional Chinese medicinal plants, the hit rates and potentiation of GABA-induced chloride currents was significantly higher than in the rest of the library. When analyzing the data according to plant parts, however, no significant difference was seen between the two subsets. In the other assays we did not find statistically significant differences in hit rates between the two subsets. Selected molecules with in vivo activity and drug-like physicochemical properties from this screening campaign will be presented and discussed.