THE APICOPLAST: A NEW TARGET FOR ANTI-MALARIAL DRUGS

描述（由申请人提供）：每年超过5亿人 感染疟疾，200万至300万儿童死于该病。40多 世界人口的10%生活在疟疾流行地区， 全球化的世界经济和旅行，人们从疟疾免费 越来越多的国家受到这种疾病的影响。疟疾寄生虫 对目前的药物迅速产生耐药性，新的药物几乎没有活性。 主要制药公司的药物发现。已经尝试过疫苗 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 顶质体-叶绿体起源的疟疾细胞器。我们有初步的 支持我们假设叶绿体毒素杀死寄生虫的数据。的 第一阶段工作的目标是提供必要的数据， 原则是：1）叶绿体衍生的顶质体是一个重要的目标 用于抗疟疾药物的开发; 2）叶绿体毒物是 高级药物测试的候选人我们将评估3类这样的 具有体外抗疟疾活性除草剂，其表现出新奇的作用， 测试抗疟疾表型的活性，测试我们的先导药物- 阿特拉津在两种抗疟疾活性体内模型中的作用。 拟议商业应用：不可用

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