Parasitic diseases, caused by intestinal helminths, remain a very serious problem in both human and veterinary medicine. While searching for new nematicides we examined a series of 1,2,4-triazole derivatives 9-22, obtained during reactions of N3-substituted amidrazones with itaconic anhydride. Two groups of compounds, 9-16 and 17-22, differed in the position of the double bond on the methacrylic acid moiety. The toxicity of derivatives 9-22 and the anti-inflammatory activity of 12 and 19-22 were studied on peripheral blood mononuclear cells (PBMC). Antiproliferative activity of compounds 12 and 19-22 was tested cytometrically in PBMC cultures stimulated by phytohemagglutinin. The influence of derivatives 12 and 19-22 on the TNF-α, IL-6, IL-10 and IFN-γ production was determined by ELISA in lipopolysaccharide-stimulated PBMC cultures. Anthelmintic activity of compounds 10-22 was studied in the Rhabditis sp. nematodes model. Most compounds (11-22) proved to be non-toxic to human PBMC. Derivatives 19-22 showed anti-inflammatory activity by inhibiting the proliferation of lymphocytes. Moreover, compounds 12 and 19-22 significantly reduced the production of TNF-α and derivatives 19-21 decreased the level of INF-γ. The strongest anti-inflammatory activity was observed for compound 21. Compounds 12 and 14 demonstrated anthelmintic activity higher than albendazole and may become promising candidates for anthelmintic drugs.
Keywords: PBMC; Rhabditis sp.; amidrazone; antiparasitic activity; antiproliferative activity; nematicidal activity; nematicides; nematodes; parasitic diseases.