THE APICOPLAST: A NEW TARGET FOR ANTI-MALARIAL DRUGS

APICOPLAST：抗疟药物的新靶标

• 批准号: 6404795
• 负责人: JAMES BIGELOW
• 金额: $ 8.26万
• 依托单位: BIOMES, INC.
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-30 至 2003-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6404795
• 关键词: Plasmodium; antimalarial agents; chloroplasts; drug design /synthesis /production; drug resistance; drug screening /evaluation; herbicides; laboratory rat; malaria

DESCRIPTION (provided by applicant): Each year more than 500 million people contract malaria and between 2-3 million children die from the disease. Over 40 percent of the world's population lives in malaria endemic regions and with the globalization of the world's economy and travel, people from malaria free countries are increasingly exposed to the disease. The malaria parasite is rapidly becoming resistant to current drugs and there is little activity of new drug discovery in the major pharmaceutical companies. Vaccines have been tried but with little success to date. The world is in desperate need for new, safe and effective anti-malarial drugs. The focus of our work is targeting the apicoplast - a malarial organelle of chloroplast origin. We have preliminary data supporting our hypothesis that chloroplast poisons kill the parasite. The goal of this Phase I work is to provide the necessary data for proof of principle that: 1) the chloroplast-derived apicoplast is an important target for anti-malarial drug development; and 2) the chloroplast poisons are candidates for advanced drug testing. We will evaluate 3 classes of such herbicides for in vitro anti-malarial activity, demonstrate novelty of action, test for activity in resistant malarial phenotypes and test our lead drug - Atrazine in two in vivo models of anti-malarial activity. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE

描述（由申请人提供）：每年超过 5 亿人 感染疟疾，有 2-300 万儿童死于这种疾病。 40岁以上 世界人口的 % 生活在疟疾流行地区 世界经济和旅行全球化，人们免受疟疾困扰 各国越来越多地受到这种疾病的影响。疟原虫是 对当前药物迅速产生耐药性，并且新药物几乎没有活性 主要制药公司的药物发现。疫苗已经尝试过了 但迄今为止收效甚微。世界迫切需要新的、安全的 和有效的抗疟疾药物。我们的工作重点是针对 apicoplast - 叶绿体起源的疟疾细胞器。我们有初步的 数据支持我们的假设，即叶绿体毒物杀死寄生虫。这 第一阶段工作的目标是提供必要的数据来证明 原则是：1）叶绿体衍生的顶端质体是重要目标 用于抗疟疾药物开发； 2）叶绿体毒物是 高级药物测试的候选人。我们将评估此类的 3 类 除草剂具有体外抗疟疾活性，表现出新颖的作用， 测试抗性疟疾表型的活性并测试我们的主导药物 - 阿特拉津在两种体内模型中的抗疟疾活性。 拟议的商业应用：不可用