5 - Promising trypanocidal heterocyclic compounds of natural origin and their synthetic analogs

Abstract

Diseases caused by members of the order Trypanosomatidae include human African trypanosomiasis (HAT) and Chagas disease, caused by species of Trypanosoma brucei and Trypanosoma cruzi, respectively, as well as leishmaniasis, caused by various species of Leishmania spp. These infections belong to the so-called neglected tropical diseases group, which are a diverse group of communicable diseases that prevail in tropical and subtropical conditions in 149 countries and affect more than one billion people in addition to costing developing economies billions of dollars every year. The available pharmacotherapies for combatting these diseases are limited and associated with strong side effects, and moreover, resistances have developed against most drugs. The urgent need for new drugs against these infections has guided the search for natural products stemming from traditional medicines which historically have been used as therapeutic agents, especially in developing countries. Thus in the past decade, a huge number of trypanocidal natural compounds have been isolated and characterized. This chapter summarizes the most significant topics concerning current therapy of trypanosomiasis (Chagas disease and HAT) and presents the compound classes and chemical entities which have been identified by bioactivity-guided fractionation of active herbal or microbial extracts. The chapter mainly focuses on promising natural or semisynthetic heterocyclic compounds. Their biological activities, antiparasitic activities, and cytotoxicities are discussed here. In the few cases where their mechanisms of action have been studied in detail, the activities of the target enzymes are also given.