Marine Natural Products as Antimalarials

海洋天然产品作为抗疟药

• 批准号: 7589385
• 负责人: DEBOPAM CHAKRABARTI
• 金额: $ 19.05万
• 依托单位: UNIVERSITY OF CENTRAL FLORIDA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-02-01 至 2011-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7589385
• 关键词: Affect; Antimalarials; Biodiversity; Biological Factors; Cessation of life; Chemicals; Child; Child Mortality; Clinical Treatment; Collection; Country; Data; Development; Disease; Dose; Drug resistance; Economics; Ecosystem; Environment; Exhibits; Florida; Goals; Growth; Health; Institutes; Lead; Life; Malaria; Marines; Methods; Mission; Oceans; Outcome; Pharmaceutical Preparations; Pharmacologic Substance; Plants; Plasmodium falciparum; Population; Preclinical Drug Evaluation; Prevalence; Procedures; Public Health; Rain; Research; Research Personnel; Sampling; Source; Structure; Surface; Testing; Therapeutic; Universities; coral; cytotoxicity; density; drug discovery; experience; forest; human disease; innovation; killings; marine natural product; marine organism; meter; novel; novel therapeutic intervention; novel therapeutics; public health relevance; resistant strain; response; sedentary; small molecule libraries

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.

描述（由申请人提供）：疟疾是一种主要的全球健康状况，影响了世界一半的人口，每年杀死约200万人。疟疾的全球经济损失是巨大的。由于抗药性菌株的普遍流行，目前针对该疾病的大多数药物都是无效的。因此，迫切需要确定新的药物铅来开发针对疟疾的下一代治疗剂。海洋生物多样性特别富含新型化学实体，尚未广泛探索抗疟药。该项目将利用港口分支海洋学研究所的独特能力来从各种海洋生态系统中采购样品，通常使用载人的潜水员在3000英尺的深度中采购样品。长期目标是从海洋天然产品开发新型的疟疾疗法。该应用的目的是鉴定海洋宏观生物的抗疟疾化合物。该项目的理由是，海洋宏观生物具有很高的可能性来产生新型化学型，因为它们的多样性很高，并且没有被广泛探索用于抗疟发发育。因此，拟议的研究与NIH的使命有关，该使命与减轻人类疾病的负担有关。通过支持初步数据的指导，将追求两个具体目标：（1）屏幕3,000海洋天然产物分数，从独特的海洋生态系统中收集，因为它们能够抑制恶性疟原虫的肠内性肠内生长。 （2）使用色谱和光谱过程来定义生物活性成分的结构，并定义生物活性组件的结构。拟议的研究很重要，因为在该项目的结尾，我们希望拥有抗疟疾的“命中”组合。 公共卫生相关性：该项目将确定可以发展为疟疾疗法的药物铅的新型化学实体。