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Title: | Caenorhabditis elegans infrared-based motility assay identified new hits for nematicide drug development |
Authors: | Risi, Gastón Aguilera, Elena Ladós, Enrique Suárez, Gonzalo Carrera, Inés Álvarez, Guzmán Salinas, Gustavo |
Type: | Artículo |
Keywords: | Nematicide, Nematode, Anthelmintic, C. elegans, Arylidene ketones, Aryl hydrazine, Pathogen Box |
Issue Date: | 2019 |
Abstract: | Nematode parasites have a profound impact on humankind, infecting nearly one-quarter of the world’s population, as well as livestock. There is a pressing need for discovering nematicides due to the spread of resistance to currently used drugs. The free-living nematode Caenorhabditis elegans is a formidable experimentally tractable model organism that offers key advantages in accelerating nematicide discovery. We report the screening of drug-like libraries using an overnight high-throughput C. elegans assay, based on an automated infrared motility reader. As a proof of concept, we screened the “Pathogen Box” library, and identical results to a previous screen using Haemonchus contortus were obtained. We then screened an in-house library containing a diversity of compound families. Most active compounds had a conjugation of an unsaturation with an electronegative atom (N, O, or S) and an aromatic ring. Importantly, we identified symmetric arylidene ketones and aryl hydrazine derivatives as novel nematicides. Furthermore, one of these compounds, (1E,2E)-1,2-bis(thiophen-3-ylmethylene)hydrazine, was active as a nematicide at 25 µm, but innocuous to the vertebrate model zebrafish at 50 µm. Our results identified novel nematicidal scaffolds and illustrate the value of C. elegans in accelerating nematicide discovery using a nonlabor-intensive automated assay that provides a simple overnight readout. |
Publisher: | MDPI |
IN: | Veterinary Sciences, 2019, 6(1): 29 |
Citation: | Risi, G, Aguilera, E, Ladós, E, y otros "Caenorhabditis elegans infrared-based motility assay identified new hits for nematicide drug development". Veterinary Sciences. [en línea] 2019, 6(1): 29. 15 h. DOI: 10.3390/vetsci6010029 |
ISSN: | 2306-7381 |
License: | Licencia Creative Commons Atribución (CC - By 4.0) |
Appears in Collections: | Publicaciones académicas y científicas - Facultad de Ciencias |
Files in This Item:
File | Description | Size | Format | ||
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10.3390vetsci6010029.pdf | 14,79 MB | Adobe PDF | View/Open |
This item is licensed under a Creative Commons License