Disulfide-Reductase Inhibitors as Chemotherapeutic Agents: The Design of Drugs for Trypanosomiasis and Malaria

Viewed globally, parasitic diseases such as malaria and Chagas' cardiopathy pose an increasing threat to human health and welfare. Recognition of this problem and the challenge of synthesizing a quinine-like antimalarial agent sparked off the development of the chemical industry about 100 years ago. Our contribution deals with aspects of drug design, a young branch of pharmaceutical chemistry. As drug targets the flavoenzyme, glutathione reductase, and the recently discovered parasite enzyme, trypanothione reductase, were chosen. Based on the knowledge of the structure of these molecules, the modeling of enzyme inhibitors as potential chemotherapeutic agents against parasites has become possible. In addition, biochemical and clinical observations are considered since chemical principles of biological evolution can serve as guidelines for the pharmaceutical chemists. The picture shows two erythrocytes destroyed by malaria parasites. In the center of the photograph a parasite is just leaving its host cell through the ruptured cell membrane. Its target could be a neighboring healthy erythrocyte.