Screening of South African medicinal plants and HPLC based profiling for the identification of leads with antiprotozoal activities
A library of 300 extracts from one hundred and seven plant species, used in South African folk medicine to treat malaria were collected and screened in vitro against Plasmodium falciparum, Trypanosoma brucei rhodesiense, Trypanosoma cruzi and Leishmania donovani. Of these 102 (34.0%) exhibited more than 50% growth inhibition of one of the parasites at the screen concentration of 9.7µg/mL and were thus considered active. P. falciparum against which seventy-two plant extracts (24.0%) showed activity was the most susceptible parasite, followed by L. donovani (forty-nine, 16.3%) and T. b. rhodesiense (thirty-six, 12.0%), with T. cruzi (zero) being the least susceptible. Twenty plants (6.6%) were selected for further investigation based on activity and specificity criteria as well as on chemotaxonomic considerations. Just 350µg of the selected extracts were fractionated by analytical scale HPLC into 32 one-minute fractions in a fully automated 96 well microfractionation scheme . After drying the microfractions were subsequently tested against the parasite for which the extract had shown activity, to identify the peaks responsible for the overall activity of the extracts. HPLC hyphenated methods (MS, UV, ELSD, HRMS and offline LC-NMR) helped to identify many active substances online. Active compounds were isolated and tested against the parasites as well as human cancer cell lines to determine their cytotoxicity. Screening results as well as selected examples of activity profiling and active compounds will be shown.
References: 1. Adams et al. (2009) Nat Prod Comm. 10:1377–81.