Format

Send to

Choose Destination
Vet Sci. 2019 Mar 17;6(1). pii: E29. doi: 10.3390/vetsci6010029.

Caenorhabditis elegans Infrared-Based Motility Assay Identified New Hits for Nematicide Drug Development.

Author information

1
Worm Biology Laboratory, Institut Pasteur de Montevideo, Montevideo 11400, Uruguay. gastonrisi@gmail.com.
2
Grupo de Química Medicinal, Facultad de Ciencias, Universidad de la República, Montevideo 11400, Uruguay. eaguilera@fcien.edu.uy.
3
Worm Biology Laboratory, Institut Pasteur de Montevideo, Montevideo 11400, Uruguay. quiquelados@gmail.com.
4
Área Farmacología, Departamento de Fisiología, Facultad de Veterinaria, Universidad de la República, Montevideo 11600, Uruguay. suarezveirano@gmail.com.
5
Worm Biology Laboratory, Institut Pasteur de Montevideo, Montevideo 11400, Uruguay. inescarrera@fq.edu.uy.
6
Departamento de Ciencias Farmacéuticas, Área Farmacología, Facultad de Química, Universidad de la República, Montevideo 11800, Uruguay. inescarrera@fq.edu.uy.
7
Laboratorio de Moléculas Bioactivas-CENUR Litoral Norte, Universidad de la República, Paysandú 60000, Uruguay. guzmanalvarezlqo@gmail.com.
8
Worm Biology Laboratory, Institut Pasteur de Montevideo, Montevideo 11400, Uruguay. gsalin@fq.edu.uy.
9
Departamento de Biociencias, Facultad de Química, Universidad de la República, Montevideo 11400, Uruguay. gsalin@fq.edu.uy.

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.

KEYWORDS:

C. elegans; anthelmintic; aryl hydrazine; arylidene ketones; nematicide; nematode; “Pathogen Box”

Supplemental Content

Full text links

Icon for Multidisciplinary Digital Publishing Institute (MDPI) Icon for PubMed Central
Loading ...
Support Center