The discovery and characterization of antiprotozoal compounds from South African medicinal plants by a HPLC-based activity profiling technique.
Mokoka, Tsholofelo Abednego.
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A total of 507 plant extracts from 174 South African plant species, selected based on their traditional uses against parasitic diseases, mainly against malaria were screened against Plasmodium falciprum, Trypanosoma brucei rhodesiense, Leishmania donovani and Trypanosoma cruzi. One-hundred and seven (107) plant extracts showed more than 95% growth inhibition against one or more parasites and were considered active. The IC50 values for these plant extracts in the different assays were determined as well as cytotoxicity evaluations. Plant extracts of Hypericum aethiopicum leaves, Leonotis leonurus leaves, Ekebergia capensis fruits, Alepidea amatymbica whole plant, Asystasia gangetica leaves, Setaria megaphylla whole plant, Leonotis ocymifolia var ocymifolia leaves, Schefflera umbellifera, Salvia repens whole plant, and Tachonanthus camphorates exhibited IC50 values of 5 μg/ml, which was used as second criteria for selecting the plant extracts for phytochemical investigation. The extracts of Schkuhria pinnata, Vernonia mespilifolia and Salvia repens showed promising activity against the parasites of T. b. rhodesiense, P. falciparum and L. donovani. In a medium throughput screening, 64 extracts inhibited the growth of one or more parasites to more than 95% at a concentration of 9.7 μg/ml The most notable results are the antitrypanosomal activities of S. pinnata (IC50 value of 2.04 μg/ml) and V. mespilifolia (1.01 μg/ml). S. repens whole plant extract showed anitleishmanial activity with an IC50 value of 5.4 μg/ml and cytotoxicity tests against myoblast L6 cells resulted in an IC50 of 41.5 μg/ml. With the aid of a HPLC-based activity profiling technique four compounds (P3-1, P4-1, P4-2 and P4-3) from these three plant species were identified and characterised as the active compounds responsible for the observed activities against the parasites, T. b. rhodesiesnse, P. falciparum and L. donovani. Sesquiterpene lactones, schkuhrin I (P4-1) and schkuhrin II (P4-2) from S. pinnata and cynaropicrin (P4-3) from V. mespilifolia were isolated while 12- methoxycarnosic acid (P3-1) was isolated from S. repens. Cynaropicrin (P4-3) was the most active sesquiterpene lactone against T. b. rhodesiense (0.23 μM). However, its antiprotozoal activity might be attributed to its toxicity as indicated by cytotoxicity against rat myoblast cells (IC50 of 1.29 μM). The sesquiterpene lactones (P4-1 and P4-2) from S. pinnata showed promising activity against T. b. rhodesiense (IC50 values of 0.86 and 1.50 μM). However, compounds P4-1 and P4-2 exhibited toxic effects against rat myoblast cells with IC50 values of 5.26 and 9.03 μM. Therefore, they are not excellent candidates as lead compounds against T. b. rhodesiense. While compounds P4-1-P4-3 and P3-1 were shown to be toxic, derivatisation of the compounds, which would change the structure and render them nontoxic could be useful if the derivatised compounds show similar activity against these parasites. 12-Methoxycarnosic acid (P3-1) showed antileishmanial activity (IC50 of 0.75 μM) and cytotoxicity against L6-cells (IC50, 17.3 μM). The selectivitiy index of 23 indicates that P3-1 is moderately toxic against the rat myoblast cells. However, it is not a good potential to be considered as a lead drug against leishmaniasis but possible derivatisation of the compound could render it less toxic.