Marine Natural Products as Antimalarials

描述（由申请人提供）：疟疾是一种主要的全球健康问题，影响世界一半人口，每年造成约200万人死亡。疟疾造成的全球经济损失是巨大的。由于耐药菌株的广泛流行，目前大多数抗该病的药物无效。因此，迫切需要确定新的药物线索，以开发下一代抗疟疾疗法。海洋生物多样性特别富含新的化学实体，尚未为发现抗疟药物而进行广泛探索。该项目将利用海港海洋研究所分支的独特能力，利用载人潜水器从不同的海洋生态系统中采集样本，通常在3000英尺的深度。长期目标是从海洋天然产品中开发新的疟疾疗法。本申请的目的是从海洋大型生物中鉴定抗疟疾化合物。该项目的理由是，海洋大型生物由于其高度多样性，极有可能产生新的化学型，而且尚未广泛探索用于抗疟开发。因此，拟议的研究与NIH的使命有关，即减轻人类疾病的负担。在初步辅助数据的指导下，将实现两个具体目标：⑴筛选从独特海洋生态系统收集的3 000种最高海洋天然产品组分，以确定其抑制恶性疟原虫红细胞内生长的能力。(2)使用色谱和光谱程序解旋活性组分并确定生物活性组分的结构。拟议的研究意义重大，因为在该项目结束时，我们预计将有一个抗疟疾“命中”的组合。 公共卫生相关性：该项目将确定可以开发成疟疾治疗药物的新型化学实体。

DESCRIPTION (provided by applicant): Malaria is a major global health that affects half of the world population and kills approximately 2 million people each year. The global economic toll of malaria is enormous. Most of the current drugs against the disease are ineffective because of widespread prevalence of drug resistant strains. Therefore, it is urgent to identify new drug leads for the development of next generation of therapeutics against malaria. Marine biodiversity is particularly rich in novel chemical entities and has not been explored extensively for antimalarial drug discovery. This project will utilize unique capability of Harbor Branch Oceanographic Institute to procure samples from diverse marine ecosystems, often at a depth of 3000 ft using manned submersibles. The long-term goal is to develop novel malaria therapeutics from marine natural products. The objective of this application is to identify antimalarial compounds from marine macroorganisms. The rationale for this project is that marine macroorganisms have a very high likelihood to yield novel chemotypes because of their high diversity and have not been extensively explored for antimalarial development. Thus, the proposed research is relevant to NIH's mission that pertains to reduce the burden of human disease. Guided by supporting preliminary data two specific aims will be pursued: (1) Screen 3,000 peak marine natural product fractions, collected from unique marine ecosystems, for their ability to inhibit intraerythrocytic growth of Plasmodium falciparum. (2) Deconvolute active fractions and define the structure of bioactive components using chromatographic and spectroscopic procedures. The proposed research is significant because at the end of this project we expect to have a portfolio of antimalarial "hits". PUBLIC HEALTH RELEVANCE: This project will identify novel chemical entities that can be developed into drug leads for malaria therapy.