Mining marine microbial natural products for anthelmintics leads

描述(由申请人提供)：这是加州大学圣地亚哥分校(UCSD)生物科学系的Raffi Aroian和UCSD斯克里普斯海洋研究所的William Fenical合作的R21申请。该计划致力于新驱虫药的发现和临床前生物开发，以治疗由寄生线虫引起的单一最大类别的被忽视的热带疾病(NTDS)。这一应用中重点关注的NTD是鞭虫病和钩虫病，尽管这项研究的结果可能更广泛地适用于蛔虫病、强直线虫病、淋巴丝虫病和盘尾丝虫病。目前，可用于治疗这些影响20多亿人的疾病的药物(驱虫药)很少，有关疗效大大降低的报告正在增加。总体而言，开发新的驱虫药的努力资金严重不足，导致世界各地的医疗保健系统没有做好充分准备，无法预防和处理对少数可用药物的耐药性的发展。该计划结合了Aroian实验室广泛的生物学经验，以及20多年基于发现的海洋微生物学研究产生的化学资源。经过培养、提取和分级的1.5万多株放线菌细菌的大量集合，现在构成了一个合作项目的基础，该项目涉及在众多驱虫药生物检测中进行生物筛选。在初步测试中，发现了几个明显含有新化学实体的高活性馏分，这表明R21试点项目可能会在驱虫药发现方面取得重大进展。

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.