Editorial [ Hot Topic: Potential Targets for the Rational Design of Antiparasitic Drugs (Executive Editor: Mahmoud H. el Kouni) ]

Parasitic diseases are the foremost worldwide health problem today, particularly in the under developed countries. It is estimated that the global prevalence of some of these diseases already exceeds 60% among the more than three billion people living in parasite endemic areas. Parasitic diseases are not confined to humans but also affect many domestic and wild animals causing an enormous economic blight to already poor countries and societies. In spite of the alarming health and economic consequences of parasitic infections, these diseases are still on the rise, largely because of poor sanitation and health education, inadequate measures of control, greater use of irrigation for agricultural development, an increase and redistribution of world population, increased world travel, and the development of resistance to drugs used for chemotherapy or chemicals for the control of vectors. In addition, with the recent advent of AIDS, several parasitic diseases which previously did not constitute a major threat to human health emerged as causative agents of lethal opportunistic infections (e.g., toxoplasmosis, cryptosporidiosis). Furthermore, the high mortality rate of some of the parasitic diseases, such as malaria, cannot be ignored. Malaria causes the death of more than two million children every year. Most parasitic diseases, however, like Ascaris or Ancylostoma infections, remain neglected because their effects on human health are more subtle. At the present time, chemotherapy is still the main stay to control most parasitic diseases, since antiparasitic vaccines are not yet available. Nevertheless, the need for new drugs is crucial to prevent or combat some major parasitic infections, (e.g., trypanosomiasis), as no single effective way of controlling this disease is available, or because some serious parasitic infections (e.g., malaria) have developed resistance to presently available drugs. Most of the currently available antiparasitic drugs have been discovered empirically by screening large numbers of compounds for efficacy against parasites in animal models. Few of these drugs have been rationally designed. This is largely because, until recently, little was known about the basic biochemistry, physiology, and molecular biology of parasites and of their interactions with their hosts. The rational design of a drug is usually based on biochemical and physiological differences between pathogens and their hosts. The ideal drug target is a protein that is essential for the parasite and does not have homologues in the host. The entry of parasites into the post-genomic age raises hopes for the identification of such novel kinds of drug targets and in turn, new treatments for parasitic diseases. However powerful, this functional genomics approach will miss some of the attractive targets for the chemotherapy of parasites as many essential proteins tend to be more highly conserved between species than non-essential ones. The articles in the current issues discuss such topics and elucidate a number of the most striking differences between parasites and their mammalian host that constitute excellent potential targets for the rational design of antiparasitic chemotherapeutic regimens. In the first article, Lüscher et al. [1], using trypanosomiasis as an example, discuss several current, successful parasiticides attack targets that have close homologues in their hosts where a therapeutic window is opened only by subtle differences in the regulation of the targets, which cannot be recognized in silico. They also advocate drug targeting, i.e. uptake or activation of a drug via parasite-specific pathways, as a chemotherapeutic strategy to selectively inhibit enzymes that have equally sensitive counterparts in the host. Like most of the other parasites studied, Trypanosomes are purine auxotrophs incapable of de novo purine biosynthesis. They depend on the salvage pathways for their vital purine requirements. Therefore, selective interruption of the parasite purine transport and/or enzymes that utilize these purines are potential targets for chemotherapy. The article of Baldwin and Coworkers [2] focuses its attention on the critical role of nucleoside transport in providing vital purines for the survival of malarial parasites.........