Elucidation of the molecular mechanism underlying the anti-inflammatory activity of an effective and safe bipyrazole-based compound

Domiati, Souraya; Mehanna, Mohammad; Ragab, Hanan M.; Galil, Khaled H. Abd El; Chmaisse, Hania Nakkash; Mallah, Ahmed El

doi:10.1007/s00011-019-01225-z

Cited by 3 publications

(4 citation statements)

References 19 publications

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“…The 2-ΔΔCt method was used to determine the mRNA relative expression levels of iNOS, nNOS, COX2, TNF-α, Il-1, and Il-10. Moreover, to confirm the PCR products, a 1.2% agarose gel electrophoresis run was performed …”

Section: Methodsmentioning

confidence: 99%

Molecular Mechanics Simulations and Experimental Investigation of the Effect of Tadalafil on Various Inflammatory Pain Mediators

2022

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Purpose: Tadalafil’s exact analgesic mechanism is still unclear. The current study aimed to elucidate this mechanism in an inflammatory pain model. Methods: Computer-assisted simulation docking experiments were carried out to assess the binding of tadalafil to different ligands. The anti-inflammatory and analgesic effects of tadalafil were evaluated using formalin-induced paw edema and a von Frey filament test, respectively. The plantar paw of the mice was then dissected to quantify iNOS, nNOS, COX-2, TNFα, IL1, and IL10 gene expression levels using a real-time polymerase chain reaction. iNOS, TNFα, and COX-2 inhibition was reassessed in vitro using the ELISA technique. One-way analysis of variance followed by post hoc Tukey test or t-test was used to compare the means. Results: Docking analysis showed a superior binding score of tadalafil to COX-2, iNOS, IL-1, and TNF-α compared to that of indomethacin and morphine and a similar binding score to nNOS and IL-10 relative to that of indomethacin. In the in vivo study, tadalafil, after an hour of formalin administration, inhibited significantly paw edema, similar to indomethacin. Furthermore, it significantly increased the withdrawal force in the von Frey filament test as compared to the negative control, which was similar to the effect observed with indomethacin and morphine. The RT-PCR revealed that tadalafil reduced significantly the iNOS, COX-2, and TNF-α gene expressions but had no effect on nNOS, IL 1, and IL10. In vitro ELISA tests confirmed the inhibition of iNOS, COX-2, and TNF-α. Conclusion: Tadalafil probably exerts its analgesic effect through the simultaneous inhibition of iNOS, COX-2, and TNF-α, which is not the case with other nonsteroidal anti-inflammatory drugs. Nevertheless, further studies are required to confirm its mechanism.

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Section: Methodsmentioning

confidence: 99%

Molecular Mechanics Simulations and Experimental Investigation of the Effect of Tadalafil on Various Inflammatory Pain Mediators

2022

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“…The further development of bipyrazole chemistry opens up new, interesting perspectives and they are playing an increasingly important role in pharmaceutical research. [9][10][11][12] Particularly, 1,3'-bipyrazoles display a broad variety of therapeutic activities, which cover the range from anticancer, [13] antibacterial, [14] antiviral, [8,15] and antimalarial [8] agents to corticotropin releasing factor receptor-1 antagonists. [16] Additionally, they have been developed as pesticides, [17] lithium ionophores [18] or responsive luminophores.…”

Section: Introductionmentioning

confidence: 99%

“…The chloroquinolinyl‐1 H ‐pyrazole shown displays antimalarial activity, [8] and pyraclonil is a widely used herbicide. The further development of bipyrazole chemistry opens up new, interesting perspectives and they are playing an increasingly important role in pharmaceutical research [9–12] . Particularly, 1,3’‐bipyrazoles display a broad variety of therapeutic activities, which cover the range from anticancer, [13] antibacterial, [14] antiviral, [8,15] and antimalarial [8] agents to corticotropin releasing factor receptor‐1 antagonists [16] .…”

Section: Introductionmentioning

confidence: 99%

Pyrazolyldiazonium Salts in the Synthesis of 4‐Amino‐1,3’‐bipyrazoles

Barabash,

Ostapiuk,

Ostapiuk

et al. 2023

Eur J Org Chem

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An efficient protocol for the synthesis of fluorescent 4‐amino‐1,3′‐bipyrazoles, which are substituted at the positions N‐1′, C‐4′, C‐3 and C‐5, is described. By a two‐step synthetic strategy, an initial azo coupling of ethyl cyanoacetate and various 1‐alkylpyrazolyldiazonium chlorides gave substituted ethyl 2‐cyano‐2‐(2‐(pyrazol‐3‐yl)hydrazine‐ylidene)acetates, which were subsequently subjected to Thorpe‐Ziegler type cyclisation reactions to yield the title compounds.

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“…These heterocyclic compounds exhibit a wide range of application areas. They are known as potential antimicrobial, 1 antitumor 2 or anti-inflammatory 3 agents, they can play a role in corrosion processes 4 , behave as enzyme selective inhibitors 5 , be effective catalysts in specific chemical reactions [6][7][8][9] or substances acting as chemo-sensors for copper(II) in aqueous solution. 10 The bipyrazole compounds are also capable to form stable complexes with transition metals as copper(II), cobalt(II) and ruthenium(II).…”

Section: Introductionmentioning

confidence: 99%

A New C,C-Linked Functionalized Bipyrazole: Synthesis, Crystal Structure, Spectroscopies and DFT Studies. Evaluation of the Antibacterial Activity and Catalytic Properties

Harit¹,

Malek²,

Bouabdallah³

et al. 2022

HETEROCYCLES

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The synthesis of new C,C-linked functionalized bipyrazole is reported.Its molecular structure has been confirmed by spectroscopic and spectrometric methods and its single crystal structure determined by X-ray analysis. The ligand 2 has been subjected to DFT and TD-DFT theoretical calculations and results are consistent with the experimental chemical analyses. The compound possesses no antibacterial activity up to 256 g/mL. However, its complexes with copper(II) salts are found to be good catalysts for the oxidation of 3,5-di-tert-butylcatechol (DTBC) into 3,5-di-tert-butylquinone (DTBQ) with a rate varying from 9.58 mol•L -1 •min -1 for the 2-[Cu(MeCO2)2] complex to 5.27 mol•L -1 •min -1 for the 2-[Cu(BF4)2] complex.

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Elucidation of the molecular mechanism underlying the anti-inflammatory activity of an effective and safe bipyrazole-based compound

Cited by 3 publications

References 19 publications

Molecular Mechanics Simulations and Experimental Investigation of the Effect of Tadalafil on Various Inflammatory Pain Mediators

Molecular Mechanics Simulations and Experimental Investigation of the Effect of Tadalafil on Various Inflammatory Pain Mediators

Pyrazolyldiazonium Salts in the Synthesis of 4‐Amino‐1,3’‐bipyrazoles

A New C,C-Linked Functionalized Bipyrazole: Synthesis, Crystal Structure, Spectroscopies and DFT Studies. Evaluation of the Antibacterial Activity and Catalytic Properties

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