MOLECULAR MECHANISMS AND THERAPEUTIC APPROACHES TO THE TREATMENT OF AFRICAN TRYPANOSOMIASIS

There are only a handful of drugs available today for treating African trypanosomiasis, most of which were discovered more than forty years ago. These drugs are plagued by various problems, ranging from oral in absorption, acute toxicities, short durations of action, and low effic acies to the emergence of trypanosomal resistance. Mechanisms of antit rypanosomal action of these drugs are mostly unknown, except for eflor nithine, which is a suicide inhibitor of ornithine decarboxylase. On t he other hand, the African trypanosomes are among the most extensively studied parasitic protozoa to date. Many of their intriguing biologic al features have been well documented and can be viewed as attractive targets for antitrypanosomal chemotherapy. These features include the glycosomal functions and protein import, the trans-splicing of mRNAs, the machineries for controlled protein degradations, the polyamine met abolism, the trypanothione metabolism, the purine salvage enzymes, and the glycolipid anchor for the surface glycoproteins.