Chapter 2 - From Bench to Bedside: Natural Products and Analogs for the Treatment of Neglected Tropical Diseases (NTDs)

Abstract

Abstract Parasitic diseases are a major cause of mortality in many tropical countries, affecting hundreds of millions people, mostly associated with poor socioeconomic and hygienic environment. Diseases caused by species of the genera Trypanosoma (Human African Trypanosomiasis and Chagas disease), Plasmodium species (malaria), and Leishmania (various forms of leishmaniasis) are among the 17 “neglected tropical diseases” (NTDs) defined as such by the World Health Organization, due to the lack of enough financial investment into research and development of new drugs by most of the pharmaceutical industry and neglect of public awareness in high-income countries. Existing therapies suffer from various deficiencies, namely, high degree of toxicity and unwanted effects, limited availability and affordability, and/or problematic application under the life conditions of affected populations. Development of new, safe, and affordable drugs is therefore an urgent need. Many well-known drugs listed in the modern pharmacopoeia have their origins in nature, including, for example, quinine from the bark of the Cinchona tree for the treatment of malaria, which has been followed by the subsequent development of the synthetic derivatives chloroquine, amodiaquine, primaquine, and mefloquine. Similarly, the potent antimalarial activity of artemisinin from the herb Artemisia annua is currently used as an alternative to chloroquinine in China against resistant strains of Plasmodium and also investigated in the United States by the military forces, since malaria can quickly debilitate troops. Besides, artemisinin has led current research to focus on the development of a large number of synthetic and semisynthetic compounds, which are more active than artemisinin. In this regard, our research group has been working on chalcones derivatives as inhibitors of Mycobacterium tuberculosis (tuberculosis), Trypanosoma cruzi, and Leishmania spp., with some patents been issued [Brazil PI 0204079-4 (2004)] because of the positive effects found for the treatment of those NTDs. In this chapter, a comprehensive list of medicinal plants, marine organisms, and other natural products that have shown activity against the etiologic agents and vectors/hosts (mainly to dengue and shistosomiasis) of NTDs is provided. Also emphasis on recent developments in groups of medicinally important natural products, particularly with reference to the structure–activity studies, will be given.