Marine Natural Products as Antimalarials

描述(申请人提供)：疟疾是一种主要的全球健康疾病，影响世界一半的人口，每年导致约200万人死亡。疟疾在全球造成的经济损失是巨大的。由于耐药菌株的广泛流行，目前治疗这种疾病的大多数药物都是无效的。因此，迫切需要为下一代疟疾治疗药物的开发寻找新的药物先导。海洋生物多样性特别富含新的化学物质，还没有被广泛探索用于抗疟疾药物的发现。该项目将利用海港分院海洋研究所的独特能力，利用载人潜水器从各种海洋生态系统中获取样品，通常是在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。这项应用的目的是从海洋大型生物中鉴定抗疟疾化合物。这个项目的基本原理是，海洋大型生物很有可能产生新的化学类型，因为它们具有高度的多样性，而且还没有被广泛探索用于抗疟疾的开发。因此，拟议的研究与美国国立卫生研究院减轻人类疾病负担的使命相关。在支持初步数据的指导下，将实现两个具体目标：(1)筛选从独特海洋生态系统收集的3,000个峰值海洋天然产物组分，以了解它们抑制恶性疟原虫红细胞内生长的能力。(2)拆分活性组分，并利用层析和光谱方法确定生物活性成分的结构。这项拟议的研究意义重大，因为在这个项目结束时，我们预计会有一系列抗疟疾药物。 与公共卫生相关：该项目将确定可开发为疟疾治疗药物先导的新化学实体。

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.