Purpose: To synthesize hybrid benzimidazolyl-chalcone derivatives, evaluate their anthelmintic activity, and establish some structural elements which could lead to induction and enhancement of this activity.
Methods: A series of 1-(1H-benzimidazol-2-yl)-3-aryl-2-propen-1-one compounds (6a-z) was synthesized by condensation reaction of 2-acetylbenzimidazole with aryl and heteroaryl aldehyde derivatives. The physicochemical characterization of these benzimidazolyl-chalcones was carried out by nuclear magnetic resonance spectroscopy (1H and 13C NMR) and mass spectroscopy (MS). All compounds were screened in vitro for their nematicidal activity against Haemonchus contortus in larval development assay. The anthelmintic activities obtained were compared with those of anthelmintic reference drugs (fenbendazole and ivermectin); 1,3-diphenyl-2-propen-1-one also used as reference for chalcone.
Results: Compounds 6a, 6g, 6w and 6y showed good nematicidal activity (LC100) at 0.002 and 0.0092 μg/ml. The activity of these four benzimidazolyl-chalcones is nearly equal to that of fenbendazole. It is also interesting to know that these compounds have anti-haemonchus activity which is equal or more efficient than ivermectin. Four other compounds (6d, 6h, 6o and 6t) possess interesting anthelmintic activities at 0.68 and 0.16 μg/ml.
Conclusion: Preliminary structure-activity relationship studies revealed that arylpropenone group in position 2 of the benzimidazole ring can be considered as new pharmacophore for nematicidal activity.