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

基本信息

批准号：
9767240
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
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-15 至 2021-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9767240
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

项目摘要

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.

项目概要由真核病原体引起的被忽视和新出现的热带疾病影响着数百人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，因此，包括美国在内，我们不断努力控制、消除和提供安全。在这个 SC3 项目中，有效的治疗方案至关重要。作为潜在临床前药物的新化学实体的优化、鉴定和验证由恶性疟原虫引起的疟疾和非洲人类锥虫病的候选者 (HAT)，由 T. brucei gambiense/rhodesense 引起。我们已鉴定出一系列化学物质。在这个项目中，我们将作为进一步发现和开发的模板。采用基于结构和天然产物的药物发现方法的组合。此外，我们将从结构上表征半胱氨酸之间的分子相互作用 T. brucei 的蛋白酶药物靶标及其抑制剂成功实现了目标和目标。该项目的目标将增加对重要的结构化学型的了解抗锥虫和抗疟药物的发现，它将促进药物开发 HAT 和利什曼病的管道。