Alexander R. Surrey

Chapter 13a. Human Antiparasitic Agents

Publisher Summary This chapter describes various aspects of human antiparasitic agents. The 4-aminoquinoline resistant Plasmodium falciparum malaria is an important problem in specific areas. Effective treatment of 4-aminoquinoline resistant falciparum malaria with combinations of two or more antimalarials including chloroquine, colchicine, quinine, pyrimethamine long-acting sulfonamides, and diaminodiphenylsulfone (DDS) has been reported. A review of the mechanism of action of chloroquine is presented in the chapter. The drug interferes with the action of several enzymes, binds to melanin and DNA, stabilizes lysosomes, and blocks the sulfhydryldisulfide interchange reaction. In the presence of chloroquine-sensitive plasmodia, mouse erythrocytes concentrate chloroquine to levels more than twice as high as those parasitized by chloroquine-resistant plasmodia. Cyclization of derivatives of arylbiguanides and arylamidineureas with acetoacetic ester or acetylacetone to the corresponding pyrimidines reduced both the toxicity and anti-malarial activity. The compounds resulting from coupling sulfa drugs and pyrimidines showed antimalarial activity, which appears to be due to the intact molecule.