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

Abstract

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.

A Review of the Biological Activity of Amidrazone Derivatives

“…The 1,2,4-triazole derivative 51 , obtained from amidrazone, showed strong anthelmintic activity (2.475 µg/µL) against Rhabditis nematodes. Due to its stronger activity than albendazole and low toxicity to PBMC, compound 51 could be a candidate for the development of new anthelmintic drugs [ 46 ].…”

“…Additionally, some 1,2,4-triazole derivatives obtained by the cyclisation of amidrazones, similar to 56 – 57 , showed a strong significant anti-inflammatory activity comparable to ibuprofen’s inhibition of PHA-stimulated PBMC proliferation and TNF-α production [ 46 , 53 ].…”

Approaches, Strategies and Procedures for Identifying Anti-Inflammatory Drug Lead Molecules from Natural Products

“…Hence, the PBMC stimulation assay is widely used for assessing anti-inflammatory activity in IBD research [ 258 , 259 , 260 ]. Paprocka et al investigated the anti-inflammatory activity of five natural SMs using LPS- LPS-stimulated PBMC, which showed that all derivatives significantly inhibited the production of pro-inflammatory cytokines, TNF and IFN-γ [ 261 ]. In another study, IPX-18 suppressed the production of IFN-γ, TNF, IL-8 and IL-2, with an IC 50 value of 96.29, 103.7, 122.9 and 105.2 nM by PBMC induced with 50 ng/mL of phorbol-12-myristate-13-acetate (PMA) [ 262 ].…”

Small Molecules as Anti‐inflammatory Agents: Molecular Mechanisms and Heterocycles as Inhibitors of Signaling Pathways

“…Further, the Anthelmintic and Antiproliferative activity of compounds studied in the Rhabditis sp and PBMC cultures stimulated by phytohemagglutinin. [148] Osmaniye's group mentioned the design and synthesis of 16 new thiadiazoles as non-selective COX inhibitors. Compound 51 shows anti-inflammatory activity similar to the standard celecoxib.…”

“…Also, compounds 49 and 50 a – d significantly reduced the production of TNF‐α and the level of INF‐γ determined by ELISA in lipopolysaccharide‐stimulated PBMC cultures. Further, the Anthelmintic and Antiproliferative activity of compounds studied in the Rhabditis sp and PBMC cultures stimulated by phytohemagglutinin [148] …”