Anti-Trypanosomal Agents from a Neotropical Cloudforest


Principal Investigator: William N Setzer
Abstract: Over 18 million people in tropical and subtropical America are afflicted by American trypanosomiasis or Chagas disease. The disease is caused by the parasitic protozoan Trypanosoma cruzi, which is transmitted by Triatomid ("kissing") bugs. The parasite enters the body through the eyes, mucous membranes, or open wounds. After entering the body, the parasite burrows into cells and begins to multiply, causing rupture of the parasitized cell, and newly produced parasites are then released into the blood. In humans, symptoms of the disease include fever, swelling, and heart and brain damage, usually leading to death. There is currently no effective treatment for this disease. The purpose of this research program is to find new medicines from tropical cloudforest plants for treatment of this parasitic disease. Tropical cloudforests are incredibly diverse, and tropical plants have evolved chemical defenses to protect themselves from being consumed by insects, nematodes, fungus attack, etc. These multitudinous chemicals, developed over millions of years, have varied and diverse structures and interfere with many different biochemical targets. Our hypothesis is that tropical cloudforest plants represent a storehouse of new chemical agents that may also inhibit parasites such as Trypanosoma. These compounds may be promising drug candidates themselves, or they may serve as templates for further synthetic elaboration and optimization. Our plan of attack in this proposal is: (a) to screen our collection of tropical rainforest plant extracts for killing of the parasites in culture, (b) to test our extracts for inhibition of some key enzymes necessary for survival of the protozoa, (c) when we find active extracts, to isolate and determine the structures of the active compounds, (d) to see how active compounds bind to enzyme target molecules, and (e) to determine the effectiveness of new potential drugs a mouse model. The long-term benefit of this research project is the development of new medicines to treat patients with Chagas disease.
Funding Period: 2004-05-01 - 2009-04-30
more information: NIH RePORT