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

Bioorg Med Chem. 2017 Dec 15;25(24):6695-6706. doi: 10.1016/j.bmc.2017.11.012. Epub 2017 Nov 6.

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 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.

Keywords: Antagonist effect; Anthelmintic; Cholinergic receptors; Haemonchus contortus; Imidazo[1,2-a]pyridine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anthelmintics / chemical synthesis
  • Anthelmintics / chemistry
  • Anthelmintics / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Discovery*
  • Haemonchus / drug effects*
  • Haemonchus / metabolism
  • Molecular Structure
  • Parasitic Sensitivity Tests
  • Pyridines / chemical synthesis
  • Pyridines / chemistry
  • Pyridines / pharmacology*
  • Receptors, Cholinergic / metabolism*
  • Structure-Activity Relationship

Substances

  • Anthelmintics
  • Pyridines
  • Receptors, Cholinergic
  • imidazo(1,2-a)pyridine