Scholarlink

Background <p>Parasitic nematodes are a public health problem globally, and an economic burden on animal and plant agricultural industries. With their ability to generate drug resistance, new anthelmintic compounds must be constantly sourced.</p> Methods <p>Using the free-living nematode, <i>Caenorhabditis elegans</i>, in an infrared-based motility assay, we screened 400 compounds from two open-source, small-molecule collections distributed by the Medicines for Malaria Venture, namely, the COVID Box and Global Health Priority Box. The screening assay was first validated for worm number, DMSO concentration and final volume.</p> Results <p>Primary and secondary (time- and concentration-dependent) screens of both boxes, identified twelve compounds as hits; nine of which are known anthelmintics. Three additional bioactives, flufenerim, flucofuron and indomethacin were identified with EC<sub>50</sub> values ranging from 0.211 to 23.174 µM. Counter toxicity screens with HEK293 cells indicated varying degrees of toxicity with EC<sub>50</sub> values ranging from 0.453 to &gt; 100 µM.</p> Conclusions <p>A <i>C. elegans</i> motility assay was optimized and used to screen two recently-released, small molecule libraries. Flufenerim, flucofuron and/or indomethacin might serve as starting points for the development of new anthelmintics.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Discovery of small molecules with anthelmintic potential in the Medicines for Malaria Venture’s COVID and Global Health Priority Boxes using an infrared-based assay for Caenorhabditis elegans motility

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年10月6日

查看全文
  • Yujie Uli Sun,
  • Lawrence J. Liu,
  • Conor R. Caffrey

摘要

Background

Parasitic nematodes are a public health problem globally, and an economic burden on animal and plant agricultural industries. With their ability to generate drug resistance, new anthelmintic compounds must be constantly sourced.

Methods

Using the free-living nematode, Caenorhabditis elegans, in an infrared-based motility assay, we screened 400 compounds from two open-source, small-molecule collections distributed by the Medicines for Malaria Venture, namely, the COVID Box and Global Health Priority Box. The screening assay was first validated for worm number, DMSO concentration and final volume.

Results

Primary and secondary (time- and concentration-dependent) screens of both boxes, identified twelve compounds as hits; nine of which are known anthelmintics. Three additional bioactives, flufenerim, flucofuron and indomethacin were identified with EC50 values ranging from 0.211 to 23.174 µM. Counter toxicity screens with HEK293 cells indicated varying degrees of toxicity with EC50 values ranging from 0.453 to > 100 µM.

Conclusions

A C. elegans motility assay was optimized and used to screen two recently-released, small molecule libraries. Flufenerim, flucofuron and/or indomethacin might serve as starting points for the development of new anthelmintics.