Synthesis and evaluation of new amidrazone-derived hydrazides as a potential anti-inflammatory agents

Paprocka, Renata; Wiese-Szadkowska, Małgorzata; Helmin-Basa, Anna; Mazur, Liliana; Kutkowska, Jolanta; Michałkiewicz, Jacek; Modzelewska-Banachiewicz, Bożena; Pazderski, Leszek

doi:10.1007/s00706-018-2197-8

Cited by 9 publications

(7 citation statements)

References 26 publications

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“…Compound 57 , at a concentration of 50 µg/mL, showed no toxicity but strongly inhibited the proliferation of PBMC activated by anti-CD3 antibodies or phytohaemagglutinin by 90–99%, and the observed effects were comparable to or stronger than those of ibuprofen. The mechanism of action of derivative 57 is cell cycle arrest at the G1 phase [ 52 ].…”

Section: Resultsmentioning

confidence: 99%

A Review of the Biological Activity of Amidrazone Derivatives

et al. 2022

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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.

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Section: Resultsmentioning

confidence: 99%

A Review of the Biological Activity of Amidrazone Derivatives

et al. 2022

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“…Interestingly, PBMC are widely used as a physiological model for immunological research of parasitic infections, such as those caused by Toxoplasma gondii and others [ 43 ]. PBMC are routinely isolated from blood samples (as we describe previously in [ 44 ]) and then used in several different tests to determine the toxicity, anti-proliferative activity and anti-inflammatory activity of studied compounds. We used the cytometric method to evaluate the proliferation response to phytohemagglutinin (PHA) and immunoezymatic tests to verify the levels of proinflammatory cytokines after lipopolysaccharide (LPS) stimulation.…”

Section: Resultsmentioning

confidence: 99%

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

et al. 2022

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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.

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“…Eighty-five examined chemical compounds were obtained in the reaction of N 3substituted amidrazones with cyclic anhydrides, following methods described previously [12][13][14]. Generally, they belong to three groups depending on chemical structure (linear, 1,2,4-triazole derivatives, and cyclic imides, as shown in Figure 1).…”

Section: Predicted and Potential Predictive Variables In The Modelmentioning

confidence: 99%

“…Previous studies have demonstrated that unsubstituted amidrazones and their chloride or bromide salts exhibit good antibacterial activity. Due to our experience in the synthesis of N 3 -substituted amidrazone derivatives, compounds such as acyclic derivatives [12], 1,2,4-triazole derivatives [13] and cyclic imides [14] were selected for this research. In this study, we attempted to determine the influence of the R1 and R2 substituents and other structural factors of new N 3 -amidrazone derivatives on their antibacterial against selected strains of Gram-positive bacteria.…”

Section: Introductionmentioning

confidence: 99%

Modeling of Effectiveness of N3-Substituted Amidrazone Derivatives as Potential Agents against Gram-Positive Bacteria

Ćwiklińska-Jurkowska,

Paprocka,

Mwaura

et al. 2024

Molecules

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Prediction of the antibacterial activity of new chemical compounds is an important task, due to the growing problem of bacterial drug resistance. Generalized linear models (GLMs) were created using 85 amidrazone derivatives based on the results of antimicrobial activity tests, determined as the minimum inhibitory concentration (MIC) against Gram-positive bacteria: Staphylococcus aureus, Enterococcus faecalis, Micrococcus luteus, Nocardia corallina, and Mycobacterium smegmatis. For the analysis of compounds characterized by experimentally measured MIC values, we included physicochemical properties (e.g., molecular weight, number of hydrogen donors and acceptors, topological polar surface area, compound percentages of carbon, nitrogen, and oxygen, melting points, and lipophilicity) as potential predictors. The presence of R1 and R2 substituents, as well as interactions between melting temperature and R1 or R2 substituents, were also considered. The set of potential predictors also included possible biological effects (e.g., antibacterial, antituberculotic) of tested compounds calculated with the PASS (Prediction of Activity Spectra for Substances) program. Using GLMs with least absolute shrinkage and selection (LASSO), least-angle regression, and stepwise selection, statistically significant models with the optimal value of the adjusted determination coefficient and of seven fit criteria were chosen, e.g., Akaike’s information criterion. The most often selected variables were as follows: molecular weight, PASS_antieczematic, PASS_anti-inflam, squared melting temperature, PASS_antitumor, and experimental lipophilicity. Additionally, relevant to the bacterial strain, the interactions between melting temperature and R1 or R2 substituents were selected, indicating that the relationship between MIC and melting temperature depends on the type of R1 or R2 substituent.

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Synthesis and evaluation of new amidrazone-derived hydrazides as a potential anti-inflammatory agents

Cited by 9 publications

References 26 publications

A Review of the Biological Activity of Amidrazone Derivatives

A Review of the Biological Activity of Amidrazone Derivatives

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

Modeling of Effectiveness of N3-Substituted Amidrazone Derivatives as Potential Agents against Gram-Positive Bacteria

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