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Extracts of seventeen Salvia species used in traditional medicine in South Africa were subjected to biological testing. The potential ability to inhibit the in vitro growth/proliferation of Plasmodium falciparum (FCR-3 strain) and the cytotoxic effects on three human cancer cells [breast adenocarcinoma (MCF-7), colon adenocarcinoma (HT-29) and glioblastoma (SF-268)] and a human kidney epithelial cell line were investigated. The extracts displayed antimalarial activity with IC50 values ranging from 3.91 to 26.01 μg/ml and S. radula displaying the most favorable activity. Two compounds were subsequently isolated from the active fraction of S. radula and identified as betulafolientriol oxide and salvigenin. The two compounds displayed similar or lower antimalarial activity (IC50 values: 4.95 and 24.60 μg/ml, respectively) compared to the crude solvent extract. The concentration required to inhibit 50% of cancer cells ranged between 9.69 μg/ml and 43.65 μg/ml, and between 8.72 μg/ml and 59.12 μg/ml against the MCF-7 and SF-268 cell lines, respectively. The IC50 values determined for the HT-29 cell line ranged from 17.05 to 57.00 μg/ml, with S. lanceolata being the most active. The samples also displayed some degree of toxicity when tested against the human kidney epithelial cells, with IC50 values ranging from 12.12 to 53.34 μg/ml. The in vitro antimalarial and anticancer activities support the historic and present use of Salvia species in traditional medicine.

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As part of an International Cooperative Biodiversity Group (ICBG) program and a collaborative research project with the Natural Products Discovery Institute, twenty plant extracts were investigated for their antiproliferative and antimalarial activities. Bioassay guided fractionation of thirteen extracts led to the identification of three new antiproliferative compounds, ethyl leptaulosides A-C (5.1-5.3), six new antiplasmodial compounds, apoplanesiacarpan A and B (2.4-2.5), (±)-rhodomyrtosone F (3.1), (±)-calliviminone C (3.2), 3α-angeloyloxy-15-hydroxylabda-7,13-dien-16,15-olid-18-oic acid (4.1), 3α-angeloyloxy-15-methoxylabda-7,13-dien-16,15-olid-18-oic acid (4.2), and twenty-six known compounds. The structures of these compounds were elucidated by using a combination of 1D (1H and 13C) and 2D NMR spectroscopy, mass spectrometry, UV, IR, CD, optical rotation, and chemical modifications. Compounds 5.1 and 5.2 showed moderate antiproliferative activity against the A2780 human ovarian cancer cell line assay with IC50 values of 3 uM and 10 uM, respectively. Compound 3.1 showed potent antiplasmodial activity with an IC50 value of 100 nM, while compounds 3.2 and 4.1 showed moderate antiplasmodial activity with IC50 values of 4 uM and 10 uM, respectively. The other compounds had IC50 values larger than 20 ug/mL, and were thus either inactive or only weakly active. / Ph. D. / Plant based natural products have a long history of being used for medicinal purposes and have played an important role in the modern drug discovery program, with the best known examples being paclitaxel as an anticancer drug, and quinine and artemisinin as antimalarial drugs. Despite great progress in fighting malarial and cancer, both diseases remain difficult to combat due to emergence of drug resistance in malarial parasites and hardness to treat various types of cancer. Therefore, it is urgent to discover new antimalarial and anticancer agents to treat these deadly diseases. This research focuses on identifying new antimalarial and anticancer agents from plant extracts. Investigation of twenty plant extracts led to the isolation of three new anticancer, six new antimalarial and twenty-six known compounds. The isolation and structure elucidation of these new bioactive compounds will be discussed in this dissertation.

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