Evaluation of Anthelmintic and Anti-Inflammatory Activity of 1,2,4-Triazole Derivatives.

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 N 3 -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.