TY - JOUR
T1 - Practical high-throughput method to screen compounds for anthelmintic activity against caenorhabditis elegans
AU - Taki, Aya C.
AU - Byrne, Joseph J.
AU - Boag, Peter R.
AU - Jabbar, Abdul
AU - Gasser, Robin B.
N1 - Funding Information:
Funding: The present study was supported by the Australian Research Council (ARC), Phylumtech (Argentina) and Yourgene Health p/l (Singapore).
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/7
Y1 - 2021/7
N2 - In the present study, we established a practical and cost-effective high throughput screening assay, which relies on the measurement of the motility of Caenorhabditis elegans by infrared light-interference. Using this assay, we screened 14,400 small molecules from the “HitFinder” library (Maybridge), achieving a hit rate of 0.3%. We identified small molecules that reproducibly inhibited the motility of C. elegans (young adults) and assessed dose relationships for a subset of compounds. Future work will critically evaluate the potential of some of these hits as candidates for subsequent optimisation or repurposing as nematocides or nematostats. This high throughput screening assay has the advantage over many previous assays in that it is cost-and time-effective to carry out and achieves a markedly higher throughput (~10,000 compounds per week); therefore, it is suited to the screening of libraries of tens to hundreds of thousands of compounds for subsequent evaluation and development. The present phenotypic whole-worm assay should be readily adaptable to a range of socioeconomically important parasitic nematodes of humans and animals, depending on their dimensions and motility characteristics in vitro, for the discovery of new anthelmintic candidates. This focus is particularly important, given the widespread problems associated with drug resistance in many parasitic worms of livestock animals globally.
AB - In the present study, we established a practical and cost-effective high throughput screening assay, which relies on the measurement of the motility of Caenorhabditis elegans by infrared light-interference. Using this assay, we screened 14,400 small molecules from the “HitFinder” library (Maybridge), achieving a hit rate of 0.3%. We identified small molecules that reproducibly inhibited the motility of C. elegans (young adults) and assessed dose relationships for a subset of compounds. Future work will critically evaluate the potential of some of these hits as candidates for subsequent optimisation or repurposing as nematocides or nematostats. This high throughput screening assay has the advantage over many previous assays in that it is cost-and time-effective to carry out and achieves a markedly higher throughput (~10,000 compounds per week); therefore, it is suited to the screening of libraries of tens to hundreds of thousands of compounds for subsequent evaluation and development. The present phenotypic whole-worm assay should be readily adaptable to a range of socioeconomically important parasitic nematodes of humans and animals, depending on their dimensions and motility characteristics in vitro, for the discovery of new anthelmintic candidates. This focus is particularly important, given the widespread problems associated with drug resistance in many parasitic worms of livestock animals globally.
KW - Anthelmintic
KW - Caenorhabditis elegans
KW - High throughput screening
KW - Infrared light-interference
KW - Motility
KW - Phenotypic screen
UR - http://www.scopus.com/inward/record.url?scp=85110768929&partnerID=8YFLogxK
U2 - 10.3390/molecules26144156
DO - 10.3390/molecules26144156
M3 - Article
C2 - 34299431
AN - SCOPUS:85110768929
VL - 26
JO - Molecules
JF - Molecules
SN - 1420-3049
IS - 14
M1 - 4156
ER -