Anthelmintic Efficacy Evaluation and Mechanism of N-Methylbenzo[d]oxazol-2-amine

Parasitic roundworms cause significant sickness and mortality in animals and humans. In livestock, these nematodes have severe economic impact and result in losses in food production on a global scale. None of the currently available drugs ideally suit all treatment circumstances, and the development of drug-resistant nematode strains has become a challenge to control the infection. There is an urgent need to develop novel anthelmintic compounds. According to our previous report, N-alkylbenzo[d]oxazol-2-amines have been successfully synthesized in the laboratory via simple procedures that provide excellent yield. Of these compounds, N-alkylbenzo[d]oxazol-2-amine (1) showed the best anthelmintic activity and lowest cytotoxicity. In this study, compound 1 was assessed for its in vivo anthelmintic properties, toxicity in animals, and mode of action using molecular docking and metabolomics approaches. The results demonstrated that the in vivo anthelmintic efficiency of compound 1 was approximately half that of albendazole. The relatively low acute toxicity was categorized into chemical category 5, with an LD50 greater than 2,000 mg/kg body. Molecular docking analysis showed the T. spiralis tubulin beta chain and glutamate-gated channels might not be the main targets of compound 1. Metabolomics analysis was used to explain the effects of compound 1 on the T. spiralis adult worm. The results demonstrated that compound 1 significantly impacted the metabolism of sphingolipids and glycerophospholipids. In conclusion, the in vivo efficacy and mechanisms of action of compound 1 need more research. The bioavailability, pharmacokinetics, and absorption of this compound should be studied further to provide information for its future development.