ABSTRACT
There is a great need for the development of new and better drugs for the treatment of many parasitic diseases. Rationally based drug design against essential parasitic enzymes or pathways is now widely regarded as a viable approach. Ideally, such targets should be essential for the survival of the parasite and absent from the host. In reality, this is seldom the case (Fairlamb, 1989a). However, trypanothione metabolism meets these criteria and its importance as a target is highlighted by the fact that a number of existing trypanocidal drugs, notably the arsenicals (Fairlamb et al., 1989) and difluoromethylornithine (DFMO) (Fairlamb et al., 1987; Bellofatto et al., 1987), interfere with the metabolism and functions of this important metabolite. In addition, since trypanothione is found in all trypanosomatids examined to date, there is the potential additional bonus of developing a drug with broad-spectrum activity against all disease caused by Trypanosoma spp. and Leishmania spp. The purpose of this article is to provide an overview of recent developments in this field, with particular reference to the current strategies for the development of new trypanocidal agents based on the selective inhibition of its metabolism. The reader is referred elsewhere for more comprehensive reviews on other aspects of this subject (Fairlamb, 1988, 1989a,b; and see Chapter 45).
