Synthesis of 2-aryl substituted benzimidazoles as bifunctional agents combining antiparasitic activity with radical-scavenging properties against Trichinella infection

Purpose The aim of this research was to synthesize a series of 2-arylbenzimidazoles and evaluate their anti- Trichinella activity and free radical scavenging potential. Methods Three complementary synthetic approaches were applied, and structures were confirmed by spectroscopic methods and DFT calculations. Biological evaluation included an in vitro anti- Trichinella spiralis (T. spiralis) assay, in vitro tubulin polymerization study, antioxidant assays (superoxide anion radical scavenging, ferric reducing capacity and suppression of AAPH-induced oxidative damage of lecithin and deoxyribose), and cytotoxicity testing in BJ human fibroblasts using the MTT assay. In silico methods were used to predict lipophilicity and other physicochemical parameters for evaluating the expected bioavailability and drug-likeness. Results The compounds exhibited pronounced in vitro larvicidal activity against T. spiralis muscle larvae. At 100 μg/mL after 48 h, 4aA and its 5(6)-nitro analogue 4cA showed high efficacy (81.5% and 80.2%, respectively), while compound 5 demonstrated the strongest effect (95.7%). In tubulin polymerization assays, 4aA slightly reduced the polymerization rate compared to control, whereas 4cA and 5 significantly enhanced it. Antioxidant activity, including radical scavenging and ferric-reducing capacity, correlated with the observed anthelmintic effects. The presence of a 4-hydroxy-3,5-dimethoxyphenyl moiety contributed to both biological activities. The deoxyribose model showed the strongest consistency in the observed activities, with compound 5 displaying superior capacity to prevent oxidative degradation. Conclusion Compound 5 stands out as a promising lead for further investigation against T. spiralis.