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no / New antimalarial drugs are urgently needed to combat emerging multidrug resistant strains of malaria parasites. This Highlight focuses on plant-derived natural products that are of interest as potential leads towards new antimalarial drugs including synthetic analogues of natural compounds, with the exception of artemisinin derivatives, which are not included due to limited space. Since effective antimalarial treatment is often unavailable or unaffordable to many of those who need it, there is increasing interest in the development of locally produced herbal medicines; recent progress in this area will also be reviewed in this Highlight.

Malaria still remains one of the world’s biggest killers with more than two million people dying from the disease each year. Present drugs have become ineffective because parasites are developing resistance to most of them. Efforts are now being directed in obtaining drugs with different structural features. Plants have provided most of the antimalarial drugs so far and efforts now concentrate on screening plants for new antimalarial drugs. South Africa with its rich floral resources and ethnobotanical history is an ideal place to screen plants for antimalarial activity. The antimalarial activity of 20 extracts from 14 ethnobotanically selected South African plants was screened for antimalarial activity in vitro. Results obtained showed that most of the plants had strong antimalarial activity. IC50 values obtained with the flow cytometric method were between 0.9 and 2 µg/ml for 9 of the 10 selected extracts. This represents a very high number of extracts with very good antimalarial activity. Cytotoxicity of the most active extracts were determined against monkey kidney cells as well as a luminescent bacteria method. Results obtained had a ID50 between 35 and 100 µg/ml with the monkey kidney cell test and between 100 and 2000 µg/ml with the bacteria test. Therapeutic values ranged between 35 and 100. Extracts therefore have a poor selectivity towards Plasmodium. The dichloromethane extract from Ozoroa engleri was further purified with silica gel column chromatography, Sephadex column chromatography and HPLC. Results obtained showed at least five or six compounds responsible for the antimalarial activity of the extract, all with moderate antimalarial activity and no further efforts were undertaken to identify them. The acetone extract of Croton pseudopulchellus was then selected for isolation of active principles and was purified by silica gel column chromatography, Sephadex column chromatography and PTLC. Kaurenoic acid was isolated as one of the active principles and identified by NMR and GC-MS. Kaurenoic acid was found to have an antimalarial IC50 of 38 µg/ml, while its cytotoxicity ID50 was 35 µg/ml. Kaurenoic acid was responsible for only some of the activity found in the purified fraction and other compound(s) in the extract might have much better antimalarial activity. / Dissertation (MSc (Plant Physiology))--University of Pretoria, 2008. / Plant Science / unrestricted

no / Cryptolepine, a naturally occurring indoloquinoline alkaloid used as an antimalarial drug in Central and Western Africa, has been found to bind to DNA in a formerly unknown intercalation mode. Evidence from competition dialysis assays demonstrates that cryptolepine is able to bind CG-rich sequences containing nonalternating CC sites. Here we show that cryptolepine interacts with the CC sites of the DNA fragment d(CCTAGG)2 in a base-stacking intercalation mode.

no / The aim of this chapter is to illustrate some current developments in natural product-derived antimalarial drugs. Traditional medicines have provided two of our most important antimalarial drugs (quinine and artemisinin) and have the potential to provide many novel antimalarial lead compounds of which several examples will be discussed. In addition, well- known natural antimalarials such as artemisinin continue to be an important focus of research and there is also increasing interest in investigating natural product sources that have not been traditionally used as antimalarials such as marine species of plants and animals. Assays based on specific malaria parasite targets such as thioredoxin reductase and heat shock protein have been employed to screen extracts and/or compounds and these have resulted in the identification of a number of potentially interesting antiplasmodial agents. However, since many victims of malaria are unable to afford antimalarial drugs, another approach adopted by some charities/NGO’s is to encourage people to grow their own medicinal plants such as Artemisia annua; some recent studies on this theme will be discussed.