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：
10655612
负责人：
Ifedayo Victor Ogungbe
金额：
$ 37.3万
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/10655612
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 Disease Drug resistance Economic Development Economically Deprived Population Economics Etiology Evaluation Funding Future Generations Goals Health care facility Human In Vitro Knowledge Laboratories Leishmania Life Expectancy Medical Metabolic Modeling Molecular Target Mus Nitroreductases North America Parasites Parasitic Diseases Pathogenicity Persons Pharmaceutical Chemistry Pharmaceutical Preparations Plasmodium Populations at Risk Preclinical Drug Development Productivity Property Protozoa Public Health Research Research Project Grants Secure Series Side Solubility South America Southeastern Asia Southern Europe Structure Structure-Activity Relationship Students Tropical Disease Trypanocidal Agents Trypanosoma Trypanosoma brucei gambiense Trypanosoma cruzi United States United States National Institutes of Health World Health Organization X-Ray Crystallography absorption acute infection analog aqueous biophysical techniques care burden chemotherapy climate change cytotoxic diagnostic tool drug action drug resistance development effective therapy efficacy study experience fexinidazole fortification improved in vivo in vivo evaluation inhibitor innovation lead optimization low income country migration molecular modeling neglect new chemical entity novel pathogen preclinical study quinoline tool 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.

项目概要致病性原生动物会引起几种被忽视的、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，并对人类构成重大威胁全球公共卫生，包括美国的公共卫生。热带病的关键问题获得有效药物的机会有限、诊断工具不足以及药物开发病原体对现有药物的耐药性。因此，持续努力控制、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可作为非洲人类药物先导物的新化学实体锥虫病 (HAT) 和恰加斯病。主要目标是研究化学实体可以抑制原生动物寄生虫产生耐药性，并应用于临床硝基芳香族药物。我们预计该项目中概述的研究将推动临床前具有多种作用机制的新一代抗锥虫药物的研究。此外，我们期望该项目的目的和目标能够成功实现将产生有关抗锥虫药物的创新和基础知识。

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Discovery of an orally active nitrothiophene-based antitrypanosomal agent.

发现一种口服活性硝基噻吩类抗锥虫药。

DOI：
发表时间：
2024-01-05
期刊：
影响因子：
6.7
作者：
Ajayi, Oluwatomi;Metibemu, Damilohun S;Crown, Olamide;Adeyinka, Olawale S;Kaiser, Marcel;Shoji, Nathalie;Silva, Mariana;Rodriguez, Ana;Ogungbe, Ifedayo Victor
通讯作者：
Ogungbe, Ifedayo Victor

The pinene scaffold: its occurrence, chemistry, synthetic utility, and pharmacological importance.

蒎烯支架：它的出现、化学、合成用途和药理学重要性。