Natural Products to Anti-trypanosomal Drugs: An Overview of New Drug Prototypes for American Trypanosomiasis

Andre Gustavo Tempone; Patricia Sartorelli; Charles Mady; Fabio Fernandes

Abstract

Protozoan tropical diseases cause great suffering throughout developing countries, with high rates of morbidity and mortality. American Trypanosomiasis affects 16-18 million people in Latin America, representing a dramatic disease among symptomatic patients. Old, toxic and ineffective chemotherapeutic agents continue to be used for the treatment of Chagas disease. Since the early days of medicine, chemical substances derived from plants and animals have been used to treat human diseases. In the marine ecosystem ecological pressures, such as competition for space and predation, may have favored several invertebrate organisms to select unique metabolites with an assortment of astonishing biological activities. In terrestrial ecosystems, amphibians present a unique efficient skin secretion system with a variety of glands which produce a myriad of potent bioactive compounds such as peptides, alkaloids, biogenic amines and lipids. Plants contribute with several antitrypanosomal compounds derived mainly from their secondary metabolism. Proteins and peptides from snake venoms have also been considered as novel drug candidates, showing effective activities. In this review, we broadly discuss the epidemiology, pathology, and current treatment of Chagas disease as well as the contributions of pharmacologically tested marine invertebrate, amphibian, snake and plant compounds which have shown promising antitrypanosomal activities. We also explore these possibilities for developing new chemotherapeutics against Chagas disease.

Keywords: Peptides, toxins, marine invertebrates, amphibians, plants, Trypanosoma cruzi, Chagas disease, drugs