Lead Optimization and Mechanisms of Action of Dual-Acting Antitrypanosomal Agents

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Project Summary Pathogenic protozoans cause several neglected, persistent, and emerging tropical diseases. These diseases impact hundreds of millions of people worldwide, and they pose significant threat to global public health, including that of the United States. The key problems of tropical diseases are limited access to effective drugs, inadequate diagnostic tools, and development of drug resistance to existing drugs by the etiological agents. Hence, continued effort to control, eliminate, and provide safe and effective treatment options is crucial. In this SC1 project, our efforts will be devoted to investigating new chemical entities that can serve as drug leads for human African trypanosomiasis (HAT) and Chagas disease. The main objective is to investigate chemical entities that can suppress the development of drug resistance by protozoan parasites to clinically used nitroaromatic drugs. We envision that the studies outlined in this project will propel preclinical studies of new generation antitrypanosomal agents that possess multiple mechanisms of action. In addition, we expect that successful implementation of the aims and objectives of this project will produce innovative and fundamental knowledge on antitrypanosomal agents.