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

双效抗锥虫药物的先导化合物优化及作用机制

基本信息

批准号：
10172488
负责人：
Ifedayo Victor Ogungbe
金额：
$ 35.75万
依托单位：
JACKSON STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-07-09 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10172488
关键词：
Affect Africa African Trypanosomiasis Benznidazole Binding Biological Availability Caring Cathepsin L Cathepsins Cathepsins B Central America Chagas Disease Chemicals Clinical Communicable Diseases Communities Computers Contracts Country Developing Countries Diagnostic Disease Drug resistance Economic Development Economically Deprived Population Economics Etiology Evaluation Funding Future Generations Goals Health care facility Healthcare Human In Vitro Individual Knowledge Laboratories Leishmania Life Expectancy Medical Metabolic Modeling Molecular Target Mus Nitroreductases North America Parasites Parasitic Diseases Pathogenicity Pharmaceutical Chemistry Pharmaceutical Preparations Plasmodium Preclinical Drug Development Productivity Property Protozoa Public Health Research Research Project Grants Risk Secure Series Side Solubility South America Southeastern Asia Southern Europe Structure Structure-Activity Relationship Students Supervision Tropical Disease Trypanocidal Agents Trypanosoma Trypanosoma brucei gambiense Trypanosoma cruzi United States United States National Institutes of Health World Health Organization X-Ray Crystallography acute infection analog aqueous base biophysical techniques chemotherapy climate change cytotoxic drug development effective therapy efficacy study experience fexinidazole improved in vivo in vivo evaluation inhibitor/antagonist innovation lead optimization low income country migration molecular modeling neglect novel pathogen preclinical study quinoline tool tool development vector

项目摘要

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.

项目摘要致病性原生动物会导致几种被忽视，持久性和新兴的热带疾病。这些疾病影响了全球数亿人，他们对包括美国在内的全球公共卫生。热带疾病的关键问题获得有效药物的机会有限，诊断工具不足和药物开发病因对现有药物的抗性。因此，继续努力控制，消除，并提供安全有效的治疗选择至关重要。在这个SC1项目中，我们的努力将是致力于调查可以用作人类非洲毒品的新化学实体锥虫病（HAT）和夏加斯病。主要目的是研究化学实体可以抑制原生动物寄生虫抗药性的发展氮气药物。我们设想，该项目中概述的研究将推动临床前对具有多种作用机制的新一代抗丙糖体剂的研究。此外，我们希望成功实施该项目的目标和目标将产生有关抗脑体剂的创新和基本知识。