Novel botanical extracts and small molecule inhibitors for African Sleeping Sickness, Chagas Disease, and Visceral Leishmaniasis

Three of most devastating neglected tropical diseases – African Sleeping Sickness, Chagas Disease and the Leishmaniases – are caused by vector-borne, flagellated protozoa. An estimated 30,000 people are infected and up to 70 million are at risk of developing African Sleeping Sickness. Chagas Disease affects an estimated 7 – 8 million people primarily in Latin and South America, and is also classified as an emerging infectious disease threat in the United States. The Leishmaniases affect 10 – 12 million people in almost 100 countries. These diseases can be extremely debilitating and even fatal if untreated. However, current drug therapies have significant issues with toxicity and there are growing concerns about developing resistance. In this study, botanical extracts from plants that are used in traditional Chinese medicine were screened for inhibitory activity against the bloodstream form of T. brucei. Selected extracts were fractionated based on bioactivity to identify active pure compounds. In addition, a library of small molecules was synthesized to probe the structure of a botanically-derived compound with known anti-microbial properties. Selected extracts and compounds with low toxicity were further screened against the intracellular forms of T. cruzi and L. donovani. These screens identified several novel compounds with IC₅₀ values in the low micromolar range and low cytotoxicity that have potential to be developed into new drug therapies for these diseases.