Malaria chemotherapeutics part I: History of antimalarial drug development, currently used therapeutics, and drugs in clinical development.

Since ancient times, humankind has had to struggle against the persistent onslaught of pathogenic microorganisms. Nowadays, malaria is still the most important infectious disease worldwide. Considerable success in gaining control over malaria was achieved in the 1950s and 60s through landscaping measures, vector control with the insecticide DDT, and the widespread administration of chloroquine, the most important antimalarial agent ever. In the late 1960s, the final victory over malaria was believed to be within reach. However, the parasites could not be eradicated because they developed resistance against the most widely used and affordable drugs of that time. Today, cases of malaria infections are on the rise and have reached record numbers. This review gives a short description of the malaria disease, briefly addresses the history of antimalarial drug development, and focuses on drugs currently available for malaria therapy. The present knowledge regarding their mode of action and the mechanisms of resistance are explained, as are the attempts made by numerous research groups to overcome the resistance problem within classes of existing drugs and in some novel classes. Finally, this review covers all classes of antimalarials for which at least one drug candidate is in clinical development. Antimalarial agents that are solely in early development stages will be addressed in a separate review.