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）生物科学部的Raffi Aroian和UCSD斯克里普斯海洋研究所的William Fenical之间的一项R21合作申请。该项目致力于发现和临床前生物开发新的驱虫药物，以治疗由寄生线虫引起的被忽视的热带疾病（NTDs）。尽管本研究的结果可能应用于更广泛的领域，如蛔虫病、圆线虫病、淋巴丝虫病和盘尾丝虫病，但本研究的重点是非传染性疾病是滴虫病和钩虫病。目前，可用于治疗这些影响20多亿人的疾病的药物（驱虫药）非常少，有关疗效大大降低的报告越来越多。总的来说，开发新的驱虫药物的努力资金严重不足，这导致了一种情况，即世界卫生保健系统在预防和处理对少数可用药物产生耐药性方面准备不足。该计划结合了阿罗亚实验室丰富的生物学经验，以及20多年来以发现为基础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株放线菌细菌的大量收集，现在构成了一个合作项目的基础，该项目涉及在许多驱虫虫生物测定中进行生物筛选。在初步测试中，已经发现了几种高活性组分，显然含有新的化学实体，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.