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

项目摘要 病原性原生动物引起几种被忽视的、持续的和新出现的热带疾病。这些 疾病影响着全世界数亿人，它们对人类构成重大威胁。 全球公共卫生，包括美国。热带病的关键问题 获得有效药物的机会有限，诊断工具不足，药物开发 病原体对现有药物的耐药性。因此，继续努力控制，消除， 并提供安全有效的治疗方案至关重要。在这个SC1项目中，我们的努力将是 致力于研究新的化学实体，可以作为药物线索， 锥虫病（HAT）和恰加斯病。主要目的是研究化学实体 其可以抑制原生动物寄生虫对临床使用的药物的耐药性的发展， 硝基芳香类药物我们设想，该项目中概述的研究将推动临床前研究， 具有多种作用机制的新一代抗锥虫药物的研究。 此外，我们期望成功地执行该项目的宗旨和目标， 将产生关于抗锥虫剂的创新和基础知识。

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.