Mining marine microbial natural products for anthelmintics leads

开采海洋微生物天然产物作为驱虫药的先导

• 批准号: 8701856
• 负责人: RAFFI V AROIAN
• 金额: $ 23.25万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-02-01 至 2016-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8701856
• 关键词: Address; Adult; Affect; Ancylostoma (genus); Animals; Anthelmintics; Ascariasis; Bacteria; Biological; Biological Assay; Biological Factors; Biological Sciences; California; Chemicals; Clinical; Collection; Development; Disease; Drug usage; Filarial Elephantiases; Foundations; Goals; Health Hazards; Healthcare Systems; Heart; Hookworms; Human; Institution; International; Intestines; Laboratories; Lead; Mammalian Cell; Marines; Microbiology; Mining; Modeling; Mus; Necator americanus; Nematoda; Nematode infections; Oceanography; Old World Hookworm; Onchocerciasis; Parasites; Parasitic nematode; Pharmaceutical Preparations; Pilot Projects; Process; Reporting; Research; Resistance development; Resources; Source; Southeastern Asia; Staging; Strongyloidiasis; Testing; Therapeutic; Trichuris; Trichuris trichiura infection; Tropical Disease; Universities; Validation; Work; base; cancer therapy; chemical resource; cytotoxicity; drug discovery; experience; in vitro testing; microbial; neglect; novel; pre-clinical; prevent; programs; public health relevance; scaffold; screening; success

DESCRIPTION (provided by applicant): This is a collaborative R21 application between Raffi Aroian of the Division of Biological Sciences at the University of California, San Diego (UCSD) and William Fenical of the Scripps Institution of Oceanography, UCSD. This program addresses the discovery and preclinical biological development of new anthelmintic drugs to treat the single largest class of neglected tropical diseases (NTDs), those caused by parasitic nematodes. The NTDs of focus in this application are trichuriasis and hookworm disease, although the results of this research are likely to apply more broadly, e.g., to Ascariasis, strongyloidiasis, lymphatic filariasis, and onchocerciasis. Currently, there are very few drugs (anthelmintics) available for these diseases that affect over 2 billion people and reports of greatly reduced efficacy are mounting. In general, the effort to develop new anthelmintic drugs has been drastically underfunded, which has led to a situation where the worldwide healthcare system is ill-prepared to prevent and deal with the development of resistance to the few drugs available. This program combines the extensive biological experience of the Aroian laboratory, with the chemical resources generated in more than 20 years of discovery-based marine microbiology research. A large collection of more than 15,000 strains of actinomycete bacteria, that have been cultivated, extracted and fractionated, now form the foundation of a collaborative program involving biological screening in numerous anthelmintic bioassays. In preliminary testing, several highly active fractions, apparently containing new chemical entities, have been discovered suggesting that an R21 pilot project is likely to lead to significant advances in anthelmintic drug discovery.

描述（由申请人提供）：这是加州大学圣地亚哥分校 (UCSD) 生物科学部的 Raffi Aroian 和 UCSD 斯克里普斯海洋学研究所的 William Fenical 合作的 R21 申请。该计划致力于新型驱虫药物的发现和临床前生物开发，以治疗由寄生线虫引起的最大一类被忽视的热带病 (NTD)。本申请重点关注的 NTD 是鞭虫病和钩虫病，尽管本研究的结果可能应用更广泛，例如蛔虫病、类圆线虫病、淋巴丝虫病和盘尾丝虫病。目前，针对这些影响超过 20 亿人的疾病的药物（驱虫药）很少，而且越来越多的报告表明疗效大大降低。总体而言，开发新驱虫药物的资金严重不足，这导致全球医疗保健系统没有做好预防和应对少数可用药物耐药性发展的准备。该计划结合了 Aroian 实验室丰富的生物学经验以及 20 多年基于发现的海洋微生物学研究中产生的化学资源。经过培养、提取和分离的超过 15,000 株放线菌菌株现在构成了涉及众多驱虫生物测定中生物筛选的合作项目的基础。在初步测试中，发现了几种显然含有新化学实体的高活性组分，这表明 R21 试点项目可能会在驱虫药物发现方面带来重大进展。