U.S. Department of Defense


Date of this Version



Progress in Medicinal Chemistry - Vol. 28, edited by G.P. Ellis and G.B. West


U.S. Government Work


Malaria is the world’s most ravaging infectious disease. Rampant throughout much of the tropics and some of the temperate areas, its numbers beggar the imagination. It threatens a third of the world’s population, presently afflicts hundreds of millions of people, causes several million deaths annually and may generate as many as 92 million new clinical cases each year [ 1, 21]. Its socioeconomic drain is enormous.

The resurgence of this pestilence during the past two decades has stimulated the search for a vaccine but, despite a prodigious research effort and some cautious optimism, an effective vaccine is still far from fruition [3-10]. In the interim, there must be continued reliance on drugs for prophylaxis and therapy. Research leading to the currently available antimalarial agents has been detailed in a number of comprehensive reviews [ 11-29]. Unfortunately, most of these agents are obsolescent because of the facility with which the malarial parasite produces drug-resistant mutants [30]. The need for more effective antimalarials is therefore critical. In a search for such drugs, a small group of investigators has returned to an old, very heavily worked and seemingly exhausted mine, the 8-aminoquinolines. The evolution of an extremely promising series of new, broad-spectrum, antimalarial 8-aminoquinolines is described in this chapter. The new drugs are unique in their dual efficacy against the blood and tissue forms of the disease.