Background: Literature survey has pointed out that Benzimidazoles represent an interesting class of anthelmintics, of which several potent members were developed.

Objective: Benzimidazoles hybridized with pharmacophoric moieties possessing anthelmintic activity were designed, synthesized to be evaluated against cercaria.

Methods: Structural modification was achieved through 2- and 5-positions. Moreover, an in vitro cercarial assay was adopted to evaluate target compounds.

Results and Discussions: Biological screening revealed that compound 3h showed significant activity with a survival index of 35% at a 100 μg/mL concentration. Whereas, compounds 3a and 3c showed moderate activity, the rest of the tested compounds exhibited low activity.

Conclusion: The current study evidenced that the new hybrids "benzimidazole-thiophen-aryl" are successful as cercacidal agents. Further studies of this novel tri-ring system are suggested on adult worms of S. mansoni.