Discovery of imidazo[1,2-a]pyridine-based anthelmintic targeting cholinergic receptors of Haemonchus contortus

[Display omitted] We report the synthesis of a series of imidazo[1,2-a]pyridine-based molecules as anthelmintic against the livestock parasite Haemonchus contortus. The molecules were tested by using Larval Paralysis Test (LPT), in order to target ionic channels, as most of the prominent marketed an...

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Veröffentlicht in:Bioorganic & medicinal chemistry 2017-12, Vol.25 (24), p.6695-6706
Hauptverfasser: N'Guessan, Jean-Paul Déto Ursul, Delaye, Pierre-Olivier, Pénichon, Mélanie, Charvet, Claude L., Neveu, Cédric, Ouattara, Mahama, Enguehard-Gueiffier, Cécile, Gueiffier, Alain, Allouchi, Hassan
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Sprache:eng
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Zusammenfassung:[Display omitted] We report the synthesis of a series of imidazo[1,2-a]pyridine-based molecules as anthelmintic against the livestock parasite Haemonchus contortus. The molecules were tested by using Larval Paralysis Test (LPT), in order to target ionic channels, as most of the prominent marketed anthelminthics present such mechanism of action. The most active compound (5e) displayed paralysis on H. contortus stage 3 larvae until 31.25 µM. Effect of 5e on H. contortus cholinergic receptors (L-AChR1 and 2) was characterized via electrophysiological measurement and a rare antagonist mode of action was unveiled.
ISSN:0968-0896
1464-3391
DOI:10.1016/j.bmc.2017.11.012