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

基本信息

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
项目类别：
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

项目摘要

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）：这是加利福尼亚大学圣地亚哥分校（UCSD）生物科学系Raffi Aroian与Scripps海洋学研究所的William Fenical之间的合作R21应用。该计划介绍了新的驱虫药物的发现和临床前生物学发展，以治疗由寄生虫造成的最大一类被忽视的热带疾病（NTD）。该应用中的重点是尿尿症和钩虫疾病，尽管这项研究的结果可能更广泛地应用于cas虫病，牢固症状，淋巴性丝虫病和尾cer虫。目前，这些疾病的药物（驱虫药）很少，这些疾病影响了超过20亿人，并且报道大大降低了疗效。总的来说，开发新的驱动药物的努力已大大资金不足，这导致了这样一种情况，在这种情况下，全球医疗保健系统的准备不足以预防和应对对少数可用药物的抵抗力的发展。该计划结合了Aroian实验室的广泛生物学经验，以及在基于发现的海洋微生物学研究中产生的化学资源。已经进行了培养，提取和分级的15,000多种菌株的放线菌细菌，现在构成了一项合作计划的基础，该计划涉及许多驱虫生物测定中的生物学筛查。在初步测试中，已经发现了几个高度活跃的部分，显然包含新的化学实体，这表明R21试点项目可能会导致驱虫药物发现的重大进展。