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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.

To this day, the quest to find new drugs is still a challenge due to the growing demands of patients suffering from chronic inflammatory diseases and the need for the individualization of therapy. The aim of this research was to synthesize new 1,2,4-triazole derivatives containing propanoic acid moiety and to investigate their anti-inflammatory, antibacterial and anthelmintic activity. Compounds 3a–3g were obtained in reactions of amidrazones 1a–1g with succinic anhydride. Several analyses of proton and carbon nuclear magnetic resonance (1H NMR, 13C NMR, respectively), as well as high-resolution mass spectra (HRMS), confirmed the structures of 1,2,4-triazole derivatives 3a–3g. Toxicity, antiproliferative activity and influence on cytokine release (TNF-α: Tumor Necrosis Factor-α, IL-6: Interleukin-6, IFN-γ: Interferon-γ, and IL-10: Interleukin-10) of the compounds 3a–3g were evaluated in peripheral blood mononuclear cells culture. Moreover, mitogen-stimulated cell culture was used for biological activity tests. The antimicrobial and anthelmintic activity of derivatives 3a–3g were studied against Gram-positive and Gram-negative bacterial strains and Rhabditis sp. culture. Despite the lack of toxicity, compounds 3a–3g significantly reduced the level of TNF-α. Derivatives 3a, 3c and 3e also decreased the release of IFN-γ. Taking all of the results into consideration, compounds 3a, 3c and 3e show the most beneficial anti-inflammatory effects.

A new Au(III) complex was synthesized from an amidrazone derivative and HAuCl4. Cyclization of amidrazone moiety lead to the 1,2,4-triazolo[1,5a]pyridine ring system, followed by Au(III) chelation. The crystal and molecular structure of the final compound was studied by single crystal X-ray diffraction as well as by 1H 13C and 1H 15N HMQC- and HMBC-NMR spectroscopy, which resulted in the assignment of all detected signals. This species was tested in vitro as an antibacterial and antiproliferative agent. It exhibited good antibacterial activity against Staphylococcus aureus and was proved to be more potent than amoxicillin against Bacillus subtilis and the drug resistant strain of Klebsiella pneumoniae. In contrast, its antiproliferative properties against cancer cell lines A549, HT-29, MV-4-11 and MCF-7 were relatively low.

1H-pyrrole-2,5-dione derivatives are known for their wide range of pharmacological properties, including anti-inflammatory and antimicrobial activities. This study aimed to synthesize new 3,4-dimethyl-1H-pyrrole-2,5-dione derivatives 2a–2f in the reaction of N3-substituted amidrazones with 2,3-dimethylmaleic anhydride and evaluate their structural and biological properties. Compounds 2a–2f were studied by the 1H-13C NMR two-dimensional techniques (HMQC, HMBC) and single-crystal X-ray diffraction (derivatives 2a and 2d). The anti-inflammatory activity of compounds 2a–2f was examined by both an anti-proliferative study and a production study on the inhibition of pro-inflammatory cytokines (IL-6 and TNF-α) in anti-CD3 antibody- or lipopolysaccharide-stimulated human peripheral blood mononuclear cell (PBMC) cultures. The antibacterial activity of compounds 2a–2f against Staphylococcus aureus, Enterococcus faecalis, Micrococcus luteus, Esherichia coli, Pseudomonas aeruginosa, Yersinia enterocolitica, Mycobacterium smegmatis and Nocardia corralina strains was determined using the broth microdilution method. Structural studies of 2a–2f revealed the presence of distinct Z and E stereoisomers in the solid state and the solution. All compounds significantly inhibited the proliferation of PBMCs in anti-CD3-stimulated cultures. The strongest effect was observed for derivatives 2a–2d. The strongest inhibition of pro-inflammatory cytokine production was observed for the most promising anti-inflammatory compound 2a.

Two new 1,2,4-triazole-containing alkenoic acid derivatives were obtained from the reaction of N -phenyl-(pyridin-2-yl)carbohydrazonamide with itaconic anhydride, depending on the reaction conditions. The structures of 2-((4-phenyl-5-(pyridin-2-yl)-4 H -1,2,4-triazol-3-yl)methyl)acrylic acid or ( E )-2-methyl-3(4-phenyl-5-(pyridine-2-yl)-4 H -1,2,4-triazol-3-yl)acrylic acid were confirmed by means of 1D and 2D NMR spectroscopic data as well as by single-crystal X-ray diffraction analysis. The experiential 1 H and 13 C chemical shifts were compared with those calculated with B3LYP, EDF1, and EDF2 density functional theories. The theoretical study of the observed terminal-to-internal alkene isomerization was performed with density functional (DFT) B3LYP/6-31+G ∗ method using SM8 water and DMF solvation models. Antimicrobial activities of the newly prepared alkenoic acid derivatives were verified experimentally by a broth microdilution method.