Identification, Optimization and Structural Investigation of Antiprotozoal Agents and Molecular Target

抗原虫剂和分子靶标的鉴定、优化和结构研究

• 批准号: 10001069
• 负责人: Ifedayo Victor Ogungbe
• 金额: $ 11.33万
• 依托单位: JACKSON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-15 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10001069
• 关键词: Africa; Africa South of the Sahara; African Trypanosomiasis; Age; Alkanesulfonates; Alstonia; Antimalarials; Antiparasitic Agents; Antiprotozoal Agents; Artemisinins; Asia; Award; Binding; Biological; Carboxylic Acids; Caring; Caspase; Cathepsin L; Central America; Chemicals; Communities; Complex; Country; Coupled; Crystallography; Development; Disease; Disease model; Drug Design; Drug Targeting; Drug resistance; Economics; Fractionation; Growth; Health care facility; Human; In Vitro; Investigation; Isoxazoles; Knowledge; Lead; Leishmania; Leishmaniasis; Life Expectancy; Ligands; Malaria; Mammalian Cell; Medical; Medicine; Middle East; Molecular Structure; Molecular Target; NMR Spectroscopy; Natural Products; North America; Parasites; Parasitic Diseases; Parasitic infection; Pharmacotherapy; Plant Extracts; Plant Leaves; Plants; Plasmodium; Plasmodium falciparum; Population; Productivity; Property; Proteins; Protozoa; Public Health; Research; Research Project Grants; Resistance; Series; South America; Southeastern Asia; Southern Europe; Spectrometry; Structural Models; Structure; Structure-Activity Relationship; Supervision; Techniques; Testing; Thiazoles; Tropical Disease; Trypanosoma; Trypanosoma brucei brucei; Trypanosoma brucei gambiense; Trypanosomiasis; United States; Validation; World Health Organization; X-Ray Crystallography; analog; base; biophysical techniques; chemotherapy; climate change; cytotoxic; design; divinyl sulfone; drug candidate; drug development; drug discovery; early childhood; effective therapy; in vitro activity; in vivo; infection risk; inhibitor/antagonist; methyl acrylate; migration; molecular recognition; mortality; neglect; novel; pathogen; pre-clinical; rhodesain; scaffold; student training; tool; validation studies

Project Summary Neglected and emerging tropical diseases caused by eukaryotic pathogens impact hundreds of millions of the world's population. These diseases are largely endemic to Asia, the Middle East, Africa, South and Central America, yet they pose a significant threat to global public health, including that of the United States. Hence, continued effort to control, eliminate, and provide safe and effective treatment options is crucial. In this SC3 project, our efforts will be devoted to the optimization, identification, and validation of new chemical entities as potential pre-clinical drug candidates for malaria, caused by Plasmodium falciparum, and Human African trypanosomiasis (HAT), caused by T. brucei gambiense/rhodesiense. We have identified a series of chemical entities that will serve as templates for further discovery and development. In this project, we will employ a combination of structure-, and natural products–based drug discovery approaches. In addition, we will structurally characterize the molecular interactions between the cysteine protease-drug target from T. brucei and its inhibitors. The successful execution of the aims and objectives for this project will add to the knowledge of structural chemotypes important for antitrypanosomal and antimalarial drug discovery, and it will add to the drug development pipeline for HAT and Leishmaniasis.

项目摘要 由真核病原体引起的被忽视和新出现的热带疾病影响了数百个国家， 数以百万计的世界人口。这些疾病主要流行于亚洲、中东、 非洲、南美洲和中美洲，但它们对全球公共卫生构成重大威胁， 包括美国在内。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SC 3项目中，我们将致力于 作为潜在临床前药物的新化学实体的优化、鉴定和验证 恶性疟原虫和非洲锥虫引起的疟疾候选者 (HAT)，由T.布氏杆菌我们发现了一系列化学物质 这些实体将作为进一步发现和开发的模板。在这个项目中，我们将 采用基于结构和天然产物的药物发现方法的组合。在 此外，我们将从结构上表征半胱氨酸之间的分子相互作用， 蛋白酶-药物靶点布鲁氏菌及其抑制剂。目标的成功实现， 该项目的目标将增加结构化学型的知识， 抗锥虫和抗疟疾药物的发现，它将增加药物开发 HAT和利什曼病的管道。