Natural Sesquiterpene Lactones as Potential Trypanocidal Therapeutic Agents: A Review

Chagas' disease and Human African Trypanosomiasis are parasitic diseases that remain major health problems, mainly among the poorest and the most marginalized communities from Latin America and Africa. The scarcity of effective chemotherapy, due to the low investment in the research and development (R&D) of new drugs, together with a high incidence of side effects, and the emergence of drug resistance phenomena emphasize the urgent need for new prophylactic and therapeutic agents. Over the ages, humans have employed natural products to treat a wide spectrum of diseases. Recently, the pharmaceutical industry has focused on plant research and a large body of evidence has been collected to demonstrate the immense potential of medicinal plants as a source of bioactive compounds and lead molecules. In the field of parasitic diseases, drug development from plants has been successful for the sesquiterpene lactone (STL) artemisinin, which is employed as an antimalarial agent. STLs are a large group of naturally occurring terpenoids derived from plants that mostly belong to the Asteraceae family which exhibit a variety of skeletal arrangements and are the largest and most diverse category of natural products with an a- m6thylene-lactone motif. STLs display a broad spectrum of biological activities such as antitumor, cytotoxic, antibacterial, anthelmintic, uterus contracting, antimalarial, neurotoxic, antiprotozoal and allergic (contact dermatitis) activities. In this context, the purpose of the present review is to provide an overview of the trypanocidal activity reported for STLs against Trypanosoma cruzi and T. brucei rhodesiense over the period 1993-2015.