Bożena Modzelewska-Banachiewicz

Amidrazones are widely used in chemical synthesis, industry and agriculture. We compiled some of the most important findings on the biological activities of amidrazones described in the years 2010–2022. The data were obtained using the ScienceDirect, Reaxys and Google Scholar search engines with keywords (amidrazone, carbohydrazonamide, carboximidohydrazide, aminoguanidine) and structure strategies. Compounds with significant biological activities were included in the review. The described structures derived from amidrazones include: amidrazone derivatives; aminoguanidine derivatives; complexes obtained using amidrazones as ligands; and some cyclic compounds obtained from amidrazones and/or containing an amidrazone moiety in their structures. This review includes chapters based on compound activities, including: tuberculostatic, antibacterial, antifungal, antiparasitic, antiviral, anti-inflammatory, cytoprotective, and antitumor compounds, as well as furin and acetylocholinesterase inhibitors. Detailed information on the compounds tested in vivo, along the mechanisms of action and toxicity of the selected amidrazone derivatives, are described. We describe examples of compounds that have a chance of becoming drugs due to promising preclinical or clinical research, as well as old drugs with new therapeutic targets (repositioning) which have the potential to be used in the treatment of other diseases. The described examples prove that amidrazone derivatives are a potential source of new therapeutic substances and deserve further research.

In this study, we present a convenient method for the synthesis of oxime ethers by reacting oximes with various chlorides (alkyl, functionalized alkyl, and benzyl) and with the subsequent use of a super base—pulverized potassium hydroxide in DMSO. The reactions take place at room temperature and the products are obtained in high yields. The final products were received within 2 min to 3 h. In addition, the compounds do not require chromatographic separation. The structure elucidation of the titled compounds was performed by using ¹H NMR and ¹³C NMR spectroscopy as well as mass spectrometry. The presented method of synthesis for oxime ethers is environmentally friendly, because neither water cooling or heating of the reaction mixture/solvents (necessary for chromatographic purification) is required. The synthesis can be carried out very easily on a large scale.

The series of new hydrazide derivatives were synthesized in reactions of N³-substituted amidrazones with cyclic anhydrides as potential anti-inflammatory and antibacterial agents. The compounds were characterized by ¹H-¹³C two-dimensional NMR techniques, which revealed the presence of two tautomeric forms in DMSO-d₆ solutions, while the molecular structure of one species was confirmed by single-crystal X-ray diffraction. The anti-inflammatory effects of hydrazides on peripheral blood mononuclear cells were experimentally evaluated. Three compounds showed antiproliferative activity comparable to ibuprofen. One derivative demonstrated strong reduction of lymphocyte proliferation stimulated by anti-CD3 antibody (by 90%) and PHA, as well as low cell toxicity. The obtained compounds exhibited relatively weak antibacterial activity; they were more effective against Gram-positive bacterial strains. Graphical abstract

The resonance forms and conformational behavior of new trisubstituted N ¹ -acylamidrazones. The temperature-induced cyclization of N ¹ -acylamidrazone to 4 H -1,2,4-triazole derivative.