Toxocara canis: larvicidal activity and bioavailability analysis of 2-pyrimidinyl-hydrazone derivatives

The treatment of human toxocariasis, a parasitic zoonosis with global distribution, is based on the use of benzimidazole anthelmintic, which have limited efficacy against Toxocara spp. larvae at the tissue level. Therefore, innovation and research into candidates for the development of new drugs for toxocariasis are essential. This study aimed to assess the efficacy of pyrimidine compounds against Toxocara canis larvae, as well as their cytotoxicity and bioavailability. The screening test was performed at 1 mg/mL, in duplicate, in a microplate containing 100 T. canis larvae in RPMI-1640 medium, and the active compound was then tested at 0.5 to 0.05 mg/mL to determine the minimum larvicidal concentration. The compound (E)-2-(2-((5-nitrofuran-2-yl)methylene)hydrazinyl)pyrimidine (PNAH 8) showed 100% larvicidal activity at 1 and 0.5 mg/mL and was not cytotoxic at any concentration tested. In silico analysis showed that the compound adhered to Lipinski's "rule of five" with an excellent miLogP value of 0.6, indicating the compound's high water solubility. And the larvicidal activity of the compound was confirmed by inoculating the contents of the microplates tested on Swiss mice, which showed no migration of larvae in the tissues. The absence of cytotoxicity and adequate bioavailability in silico, comparable to albendazole, the anthelmintic of first choice for the treatment of human toxocariasis, along with the other results, suggest the potential of this compound for future investigations in preclinical tests.