Further and new target-based benzimidazole anthelmintics active against Teladorsagia circumcincta

Helminth infections are one of the most prevalent parasitic diseases affecting animals and humans worldwide. Anthelmintic resistance to main drugs used control these in animals, especially ruminants, is a major global problem that needs urgent solutions. The purpose this study was design obtain new benzimidazole (BZ) derivatives evaluate their vitro ovicidal larvicidal activities. Based on previous results from 2-phenylbenzimidazoles docking studies different BZ-containing scaffolds Teladorsagia circumcincta tubulin four structural groups BZs were selected. In addition several members those previously reported 2-phenylBZs (type I), some twenty 2-aminoBZ II) twenty-five BZ amides (types III IV) prepared evaluated for ability inhibit egg hatching larval motility T. with superior achieved. Nine fifty-five tested displayed activity higher than 90%, fourteen induced more 30% death assays at 50 µM. benzamide 42 showed best EC50 value 0.92 µM selectivity index > 100 respecting HepG2 cells, while benzylamine 13 attained 50% activity. Notably, amide 39 both (100%) (>50%) SAR analysis carried out led conclusion that, effects tubulin, pending experimental confirmation, there must be other mechanisms by which prevent limit mobility larvae.