Discovery of imidazo[1, 2-a]pyridine-based anthelmintic targeting cholinergic receptors of Haemonchus contortus. Issue 24 (15th December 2017)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Bioorganic & medicinal chemistry. Volume 25:Issue 24(2017)
• Page Start: 6695
• Page End: 6706
• Publication Date: 2017-12-15
• Subjects: Imidazo[1, 2-a]pyridine -- Anthelmintic -- Haemonchus contortus -- Cholinergic receptors -- Antagonist effect; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2017.11.012
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: 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 of5e on H. contortus cholinergic receptors (L-AChR1 and 2) was characterized via electrophysiological measurement and a rare antagonist mode of action was unveiled.