Drug resistance in Plasmodium: natural products in the fight against malaria

Malaria, perhaps one of the most serious and widespread diseases encountered by mankind, continues to be a major threat to about 40 % of the world's population, especially in the developing world. As malaria vaccines remain problematic, chemotherapy still is the most important weapon in the fight against the disease. However, almost all available drugs have been compromised by the highly adaptable parasite, and the increasing drug resistance of Plasmodium falciparum continues to be the main problem. Therefore, the limited clinical repertoire of effective drugs and the emergence of multi-resistant strains substantiate the need for new anti-malarials. Plant-derived artemisinin is currently the only available drug that is globally effective, but alarmingly, recent studies suggest that resistance already may be developing. Nevertheless, the success story of artemisinin from the herb Qing Hao (Artemisia annua L.), used as a remedy in traditional Chinese medicine for more than two thousand years, shows once again that natural products serve as an invaluable reservoir of lead compounds for sophisticated small molecules. This review outlines the major anti-malarials, summarizing recent knowledge about their mode of action and the development of drug resistance. Furthermore, the most promising and recently discovered natural products with anti-malarial potential will be introduced.