Novel compounds to combat trypanosomatid infections: a medicinal chemical perspective

INTRODUCTION: The current therapeutic arsenal against the kinetoplastids Trypanosoma brucei, Trypanosoma cruzi and Leishmania spp. is clearly inadequate and underscores the urgent need to develop new effective, safe and cost-effective drugs. AREAS COVERED: Accordingly, this review of patented products and processes using anti-kinetoplastid agents provides insight into the identification of novel or more refined drugs. In this review, we describe products developed in recent years for the treatment of human African trypanosomiasis, American trypanosomiasis and leishmaniasis from a medicinal chemical perspective. EXPERT OPINION: Applications so far have looked only superficially for candidate anti-trypanosomatid drugs and are deficient in the final stages of drug development studies, i.e., tolerance/safety, selectivity, drug-resistance, scaling-up, pharmacokinetic and pharmacodynamic assays. The ultimate goal for production of agents with anti-HAT activity has been the development of dicationic agents with parasite DNA-binding activity. Another goal for control of human African trypanosomiasis as well as for Chagas disease and leishmaniasis is the development of protease inhibitors. It should also be noted that several recent studies describing promising targets and compounds have not yet been patented. An effort should be made by foundations, international health organizations and pharmaceutical corporations to support analysis and development of promising new chemotherapeutic agents for controlling the trypanosomiasis and leishmaniasis.